11,496 results on '"Innate immunity"'
Search Results
2. Human milk affects TLR4 activation and LPS-induced inflammatory cytokine expression in Caco-2 intestinal epithelial cells.
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Pizzarello, Catherine R., Nelson, Ashley, Verekhman, Ilya, Seppo, Antti E., and Järvinen, Kirsi M.
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Human milk (HM) components affect immune cell toll-like receptor 4 (TLR4) signaling. However, studies examining the immunomodulatory impacts of HM on TLR4 signaling in intestinal epithelial cells (IECs) are limited. This study utilized both a TLR4 reporter cell line and a Caco-2 IEC model to examine the effects of HM on lipopolysaccharide (LPS)-induced TLR4 activation and cytokine responses, respectively. Additionally, we performed fast protein liquid chromatography and mass spectrometry to identify a HM component that contributes to the effect of HM on LPS/TLR4 signaling. HM enhances LPS-induced TLR4 signaling as well as LPS-induced IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Human serum albumin (HSA) present in HM contributes to these effects. HSA within HM synergizes with LPS to induce IEC gene expression of pro-inflammatory cytokines and negative regulators of NF-κB. Altogether, this study provides mechanistic evidence behind the immunomodulatory function of HM on IECs, which may contribute to an enhanced immune response in breast-fed neonates. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Poly (I:C)-Induced microRNA-30b-5p Negatively Regulates the JAK/STAT Signaling Pathway to Mediate the Antiviral Immune Response in Silver Carp (Hypophthalmichthys molitrix) via Targeting CRFB5.
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Liu, Meng, Tang, Huan, Gao, Kun, Zhang, Xiqing, Ma, Zhenhua, Jia, Yunna, Yang, Zihan, Inam, Muhammad, Gao, Yunhang, Wang, Guiqin, and Shan, Xiaofeng
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In aquaculture, viral diseases pose a significant threat and can lead to substantial economic losses. The primary defense against viral invasion is the innate immune system, with interferons (IFNs) playing a crucial role in mediating the immune response. With advancements in molecular biology, the role of non-coding RNA (ncRNA), particularly microRNAs (miRNAs), in gene expression has gained increasing attention. While the function of miRNAs in regulating the host immune response has been extensively studied, research on their immunomodulatory effects in teleost fish, including silver carp (Hyphthalmichthys molitrix), is limited. Therefore, this research aimed to investigate the immunomodulatory role of microRNA-30b-5p (miR-30b-5p) in the antiviral immune response of silver carp (Hypophthalmichthys molitrix) by targeting cytokine receptor family B5 (CRFB5) via the JAK/STAT signaling pathway. In this study, silver carp were stimulated with polyinosinic-polycytidylic acid (poly (I:C)), resulting in the identification of an up-regulated miRNA (miR-30b-5p). Through a dual luciferase assay, it was demonstrated that CRFB5, a receptor shared by fish type I interferon, is a novel target of miR-30b-5p. Furthermore, it was found that miR-30b-5p can suppress post-transcriptional CRFB5 expression. Importantly, this study revealed for the first time that miR-30b-5p negatively regulates the JAK/STAT signaling pathway, thereby mediating the antiviral immune response in silver carp by targeting CRFB5 and maintaining immune system stability. These findings not only contribute to the understanding of how miRNAs act as negative feedback regulators in teleost fish antiviral immunity but also suggest their potential therapeutic measures to prevent an excessive immune response. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Immune functions of C‐type lectins in medical arthropods.
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Ming, Zhihao, Chen, Zhiqiang, Tong, Hao, Zhou, Xia, Feng, Tingting, and Dai, Jianfeng
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PHENOL oxidase , *ARTHROPODA , *LECTINS , *ANIMAL diseases , *CALCIUM ions , *LIGANDS (Biochemistry) - Abstract
C‐type lectins (CTLs) are a family of proteins that contain 1 or more carbohydrate‐recognition domains (CRDs) and bind to a broad repertoire of ligands in the presence of calcium ions. CTLs play important roles in innate immune defenses against microorganisms by acting as pattern‐recognition receptors (PRRs) for invading pathogens, such as bacteria, viruses, and parasites. After binding to pathogen‐associated ligands, CTLs mediate immune responses, such as agglutination, phagocytosis, and the activation of phenol oxidase progenitors, thereby clearing pathogens. CTLs are an evolutionarily conserved family found in almost all vertebrates and invertebrates. Medical arthropods can acquire and transmit a range pathogens through various approaches, such as bloodsucking, lancing, and parasitism, thus infecting humans and animals with related diseases, some of which can be life‐threatening. Recent studies have shown that lectins are important components of the arthropod immune system and are essential for the immune responses of arthropods to arthropod‐borne pathogens. This article reviews the current understanding of the structure, function, and signaling pathways involved in CTLs derived from important medical arthropods. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Role of Complement Components in Asthma: A Systematic Review.
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Tornyi, Ilona and Horváth, Ildikó
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Background: Asthma is a chronic inflammatory airway disease characterized by recurrent symptoms in response to a wide range of external stimuli, including allergens, viral infections, and air pollution together with internal host-derived danger signals. The disease is traditionally associated with adaptive immune responses; recent research emphasizes the critical role of innate immunity in its pathogenesis. The complement system, activated as part of the defense mechanisms, plays a crucial role in bridging innate to adaptive immunity. While experimental models demonstrate complement cascade activation in asthma, human studies remain limited. Methods: This systematic review summarizes existing literature on the complement system in asthma patients, gathering data from PubMed, Web of Science, Scopus, and Google Scholar. The protocol was registered in the OSF. Results: Out of 482 initially identified articles, only 24 met the eligibility criteria, revealing disparities in sample origin, methodologies, and populations. Despite observed heterogeneity, a consistent result was found in the elevation of complement regulatory proteins, such as complement Factor H, in samples from patients with asthma compared to those from healthy subjects. Conclusions: The increased level of regulatory proteins, such as Factor H and I highlight that these may influence asthma pathophysiology. The role of complement factors as potential biomarkers of asthma activity and severity needs further evaluation. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Role of Medaka (Oryzias latipes) Foxo3 in Resistance to Nervous Necrosis Virus Infection.
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Li, Wen, Wang, Zhi, Liang, Jingjie, Xia, Bilin, Chen, Ruoxue, and Chen, Tiansheng
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Simple Summary: In this study, we investigated the survival rate and the expression of interferon-related genes of medaka (Oryzias latipes) foxo3 mutants compared to WT after RGNNV challenge. This will be used for the study of disease resistance immunity-related genes in teleost. Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the IFN-guided immune response in fish is yet to be clarified. In this study, we characterized foxo3 in Japanese medaka (Oryzias latipes) and examined its role in the IFN-dependent immune response upon infection with the RGNNV. The results show that the coding region of the medaka foxo3 gene is 2007 base pairs long, encoding 668 amino acids, and possesses a typical forkhead protein family structural domain. The product of this gene shares high homology with foxo3 in other fish species and is widely expressed, especially in the brain, eyes, testes, and heart. Upon RGNNV infection, foxo3−/− mutant larvae showed a lower mortality rate, and adults exhibited a significant reduction in virus replication. Moreover, the absence of foxo3 expression led to an increase in the expression of irf3, and a decrease in the expression of other IFN-related genes such as tbk1 and mapk9, implying that foxo3 may function as a negative regulator in the antiviral signaling pathway. These findings provide crucial insights for disease-resistant breeding in the aquaculture industry. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Effects of Akt Activator SC79 on Human M0 Macrophage Phagocytosis and Cytokine Production.
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Lee, Robert J., Adappa, Nithin D., and Palmer, James N.
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Akt is an important kinase in metabolism. Akt also phosphorylates and activates endothelial and neuronal nitric oxide (NO) synthases (eNOS and nNOS, respectively) expressed in M0 (unpolarized) macrophages. We showed that e/nNOS NO production downstream of bitter taste receptors enhances macrophage phagocytosis. In airway epithelial cells, we also showed that the activation of Akt by a small molecule (SC79) enhances NO production and increases levels of nuclear Nrf2, which reduces IL-8 transcription during concomitant stimulation with Toll-like receptor (TLR) 5 agonist flagellin. We hypothesized that SC79's production of NO in macrophages might likewise enhance phagocytosis and reduce the transcription of some pro-inflammatory cytokines. Using live cell imaging of fluorescent biosensors and indicator dyes, we found that SC79 induces Akt activation, NO production, and downstream cGMP production in primary human M0 macrophages. This was accompanied by a reduction in IL-6, IL-8, and IL-12 production during concomitant stimulation with bacterial lipopolysaccharide, an agonist of pattern recognition receptors including TLR4. Pharmacological inhibitors suggested that this effect was dependent on Akt and Nrf2. Together, these data suggest that several macrophage immune pathways are regulated by SC79 via Akt. A small-molecule Akt activator may be useful in some infection settings, warranting future in vivo studies. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Inflammasomes in epithelial innate immunity: front line warriors.
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Robinson, Kim Samirah and Boucher, Dave
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NATURAL immunity , *INFLAMMASOMES , *CELL death , *HOMEOSTASIS , *IMMUNE response , *TOLL-like receptors , *GASTROINTESTINAL system - Abstract
Our epithelium represents a battle ground against a variety of insults including pathogens and danger signals. It encodes multiple sensors that detect and respond to such insults, playing an essential role in maintaining and defending tissue homeostasis. One key set of defense mechanisms is our inflammasomes which drive innate immune responses including, sensing and responding to pathogen attack, through the secretion of pro‐inflammatory cytokines and cell death. Identification of physiologically relevant triggers for inflammasomes has greatly influenced our ability to decipher the mechanisms behind inflammasome activation. Furthermore, identification of patient mutations within inflammasome components implicates their involvement in a range of epithelial diseases. This review will focus on exploring the roles of inflammasomes in epithelial immunity and cover: the diversity and differential expression of inflammasome sensors amongst our epithelial barriers, their ability to sense local infection and damage and the contribution of the inflammasomes to epithelial homeostasis and disease. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Liquid–liquid phase separation in innate immunity.
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Liu, Dawei, Yang, Jinhang, and Cristea, Ileana M.
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NATURAL immunity , *PHASE separation , *POST-translational modification , *STRESS granules , *CELL anatomy , *INFLAMMASOMES - Abstract
Liquid–liquid phase separation (LLPS) has emerged as a key mechanism regulating innate immunity, and dynamically organizing immune factors to achieve rapid responses. LLPS tightly regulates DNA and RNA sensing pathways, inflammasome activation, as well as stress granule and PML nuclear body formation. Viruses dysregulate or exploit LLPS mechanisms to evade host defenses and promote infection. Post-translational modifications, such as phosphorylation and acetylation, provide dynamic regulatory toggles for LLPS, dictating the formation and disassembly of biomolecular condensates in immune cell signaling for rapid and plastic responses. Liquid–liquid phase separation (LLPS) has emerged as a crucial mechanism for orchestrating innate immune responses. LLPS facilitates the dynamic organization of cellular components for enhanced specificity and efficiency of pathogen detection and immune activation. Understanding such LLPS-mediated regulatory mechanisms in innate immunity offers an important perspective into rapid and coordinated host defense responses and points to potential therapeutic targets for diseases characterized by immune dysfunction or viral immune evasion. Intrinsic and innate immune responses are essential lines of defense in the body's constant surveillance of pathogens. The discovery of liquid–liquid phase separation (LLPS) as a key regulator of this primal response to infection brings an updated perspective to our understanding of cellular defense mechanisms. Here, we review the emerging multifaceted role of LLPS in diverse aspects of mammalian innate immunity, including DNA and RNA sensing and inflammasome activity. We discuss the intricate regulation of LLPS by post-translational modifications (PTMs), and the subversive tactics used by viruses to antagonize LLPS. This Review, therefore, underscores the significance of LLPS as a regulatory node that offers rapid and plastic control over host immune signaling, representing a promising target for future therapeutic strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Therapy-naïve malignancy causes cardiovascular disease: a state-of-the-art cardio-oncology perspective.
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Ogilvie, Leslie M., Coyle-Asbil, Bridget, Brunt, Keith R., Petrik, Jim, and Simpson, Jeremy A.
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CARDIO-oncology , *CARDIOVASCULAR diseases , *EXPOSURE therapy , *DISEASE risk factors , *HEART failure , *CANCER invasiveness - Abstract
Cardiovascular disease (CVD) and cancer are the leading causes of mortality worldwide. Although generally thought of as distinct diseases, the intersectional overlap between CVD and cancer is increasingly evident in both causal and mechanistic relationships. The field of cardio-oncology is largely focused on the cardiotoxic effects of cancer therapies (e.g., chemotherapy, radiation). Furthermore, the cumulative effects of cardiotoxic therapy exposure and the prevalence of CVD risk factors in patients with cancer lead to long-term morbidity and poor quality of life in this patient population, even when patients are cancer-free. Evidence from patients with cancer and animal models demonstrates that the presence of malignancy itself, independent of cardiotoxic therapy exposure or CVD risk factors, negatively impacts cardiac structure and function. As such, the primary focus of this review is the cardiac pathophysiological and molecular features of therapy-naïve cancer. We also summarize the strengths and limitations of preclinical cancer models for cardio-oncology research and discuss therapeutic strategies that have been tested experimentally for the treatment of cancer-induced cardiac atrophy and dysfunction. Finally, we explore an adjacent area of interest, called "reverse cardio-oncology," where the sequelae of heart failure augment cancer progression. Here, we emphasize the cross-disease communication between malignancy and the injured heart and discuss the importance of chronic low-grade inflammation and endocrine factors in the progression of both diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Carbohydrate-binding ability of a recombinant protein containing the DM9 motif from Drosophila melanogaster.
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Hatakeyama, Tomomitsu, Kojima, Fuki, Ohkawachi, Issei, Sawai, Hitomi, and Unno, Hideaki
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DROSOPHILA melanogaster , *RECOMBINANT proteins , *PLANT lectins , *CARBOHYDRATE-binding proteins , *ISOTHERMAL titration calorimetry , *COLUMNS , *GLYCANS - Abstract
Proteins containing DM9 motifs, which were originally identified in the Drosophila melanogaster genome, are widely distributed in various organisms and are assumed to be involved in their innate immune response. In this study, we produced a recombinant protein of CG13321 (rCG13321) from D. melanogaster , which consists of four DM9 motifs, in Escherichia coli cells. In affinity chromatography using a mannose-immobilized column, rCG13321 exhibited mannose-binding ability and was separated into high-affinity and low-affinity fractions, named HA and LA, respectively, based on its binding ability to the column. In addition to having a higher affinity for the column, HA exhibited self-oligomerization ability, suggesting slight differences in tertiary structure. Both LA and HA showed hemagglutinating activity and were able to agglutinate an oligomannose-containing dendrimer, indicating that they have multiple carbohydrate-binding sites. Glycan array analysis suggested that rCG13321 primarily recognizes d -mannose and d -rhamnose through hydrogen bonding with the 2-, 3- and 4-hydroxy groups. Isothermal titration calorimetry demonstrated that rCG13321 has a comparable affinity to typical lectins. These findings suggest that CG13321 functions as a carbohydrate-binding protein or lectin that recognizes mannose and related carbohydrate-containing molecules on the surface of foreign organisms as a pattern recognition molecule. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Novel BRICHOS-related Defensin-like Antimicrobial Peptide from the Marine Polychaeta Arenicola marina.
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Safronova, V. N., Panteleev, P. V., Kruglikov, R. N., Bolosov, I. A., Finkina, E. I., and Ovchinnikova, T. V.
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ANTIMICROBIAL peptides , *AMINO acid residues , *PROTEIN precursors , *PEPTIDES , *PEPTIDE antibiotics , *BACTERIAL cell walls , *DEFENSINS - Abstract
Objective: To date, polychaetes remain a poorly studied class of invertebrate animals in terms of the features of functioning of their immune system and, in particular, the biodiversity of antimicrobial peptides (AMPs). AMPs also known as host defense peptides play a key role in host protection from various pathogens and regulation of the species composition of symbiotic microbes. A study of the biosynthesis of AMPs in polychaetes resulted in the discovery of the so-called BRICHOS domain in the structure of the precursor proteins of a number of such peptides. The conserved structure of this domain makes possible the bioinformatic search for AMP precursors in polychaete transcriptomes. In this work, we found and studied a novel BRICHOS-related AMP from the lugworm Arenicola marina, representing a previously undiscovered in polychaetes a structural family of defensin-like peptides stabilized by four disulfide bonds. Methods: The peptide, designated as AmBRI-44a and containing 44 amino acid residues, was obtained by heterologous expression in Escherichia coli. The peptide secondary structure was investigated by CD spectroscopy in water and dodecylphosphocholine (DPC) micelles. The minimum inhibitory concentrations (MICs) against a wide range of bacterial pathogens were assessed using the two-fold serial dilutions method. Cytotoxicity of AmBRI-44a was studied in vitro on human erythrocytes or adherent cell line HEK293T using the hemoglobin release assay or the MTT test, respectively. The AMBRI-44a potential target was discovered by successive daily subculturing of the AmBRI-44a resistant strain followed by whole-genome sequencing. Results and Discussion: According to CD data, AmBRI-44a is a predominantly β-structured peptide. AmBRI-44a was shown to have a specific activity against a narrow spectrum of Gram-positive bacteria and pronounced cytotoxic effects on the eukaryotic cell line HEK293T. The proposed mechanism of the antibacterial action of this peptide is associated with the inhibition of bacterial cell wall biosynthesis, as indicated by the genetic and phenotypic analysis of selected AmBRI-44a-resistant bacteria Bacillus licheniformis B-511. Conclusions: The resulting data allow us to consider the discovered peptide AmBRI-44a as a candidate compound for the development of an antibiotic agent that could potentially be effective in the treatment of infectious diseases mediated by multidrug-resistant Gram-positive bacteria. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Mapping the immune cell landscape of severe atopic dermatitis by single‐cell RNA‐seq.
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Jin, Seon‐Pil, Lee, Kyungchun, Bang, Yoon Ji, Jeon, Yun‐Hui, Jung, Sunyoung, Choi, So‐Jung, Lee, Ji Su, Kim, Junhan, Guttman‐Yassky, Emma, Park, Chung‐Gyu, Kim, Hyun Je, Hong, Seunghee, and Lee, Dong Hun
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ATOPIC dermatitis , *MONONUCLEAR leukocytes , *INNATE lymphoid cells , *ECZEMA , *TH2 cells , *RNA sequencing - Abstract
Background: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. Methods: Employing single‐cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. Results: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2‐priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. Conclusion: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Ontogeny of myeloperoxidase (MPO) positive cells in flounder (Paralichthys olivaceus).
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Gan, Qiujie, Chi, Heng, Liang, Chengcheng, Zhang, Letao, Dalmo, Roy Ambli, Sheng, Xiuzhen, Tang, Xiaoqian, Xing, Jing, and Zhan, Wenbin
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PARALICHTHYS , *MYELOPEROXIDASE , *FLATFISHES , *NEUTROPHILS , *WESTERN immunoblotting , *ONTOGENY , *FISH development , *MESSENGER RNA - Abstract
Neutrophils represent an important asset of innate immunity. Neutrophils express myeloperoxidase (MPO) which is a heme-containing peroxidase involved in microbial killing. In this study, by using real-time quantitative PCR and Western blot analysis, the flounder MPO (Po MPO) was observed to be highly expressed in the head kidney, followed by spleen, gill, and intestine during ontogeny – during developmental stages from larvae to adults. Furthermore, Po MPO positive cells were present in major immune organs of flounder at all developmental stages, and the number of neutrophils was generally higher as the fish grew to a juvenile stage. In addition, flow cytometry analysis revealed that the proportion of Po MPO positive cells relative to leukocytes, in the peritoneal cavity, head kidney, and peripheral blood of flounder juvenile stage was 18.3 %, 34.8 %, and 6.0 %, respectively, which is similar to the adult stage in flounder as previously reported. The presence and tissue distribution of Po MPO during ontogeny suggests that Po MPO positive cells are indeed a player of the innate immunity at all developmental stages of flounder. • MPO transcripts and protein were first detected at 1-day post-hatch in flounder. • MPO was widely expressed in the immune related organs. • MPO+ cells exist in all developmental stages and increase in number as flounder grow. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Molecular characterization, immune functions and DNA protective effects of peroxiredoxin-1 gene in Antheraea pernyi.
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Abbas, Muhammad Nadeem, Gul, Isma, Khosravi, Zahra, Amarchi, Jemirade Ifejola, Ye, Xiang, Yu, Lang, Siyuan, Wu, and Cui, Hongjuan
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RECOMBINANT proteins , *AMINO acid residues , *PEROXIREDOXINS , *DNA , *GENES , *OXIDATIVE stress - Abstract
Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H 2 O 2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H 2 O 2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H 2 O 2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H 2 O 2 in ApPrx-1 -depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects. • Prx-1 gene was identified from the Chinese oak silkworm, A. pernyi. • Microbial challenges modulate the expression patterns of ApPrx-1 in immune tissues. • Recombinant ApPrx-1 protein protects supercoiled DNA damage from oxidative stress. • Silencing of ApPrx-1 strongly affected the H 2 O 2 and bacterial clearance in A. pernyi. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Role and molecular mechanism of NOD2 in chronic non-communicable diseases.
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Kong, Lingjun, Cao, Yanhua, He, Yanan, and Zhang, Yahui
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PATTERN perception receptors , *CROHN'S disease , *NON-communicable diseases , *CONSERVED sequences (Genetics) , *CHRONIC diseases , *AUTOIMMUNE diseases , *AMINO acid sequence - Abstract
Nucleotide-binding oligomerization domain containing 2 (NOD2), located in the cell cytoplasm, is a pattern recognition receptor belonging to the innate immune receptor family. It mediates the innate immune response by identifying conserved sequences in bacterial peptide glycans and plays an essential role in maintaining immune system homeostasis. Gene mutations of NOD2 lead to the development of autoimmune diseases such as Crohn's disease and Blau syndrome. Recently, NOD2 has been shown to be associated with the pathogenesis of diabetes, cardiac-cerebral diseases, and cancers. However, the function of NOD2 in these non-communicable diseases (CNCDs) is not well summarized in reviews. Our report mainly discusses the primary function and molecular mechanism of NOD2 as well as its potential clinical significance in CNCDs. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Effect of long-term dietary supplementation with lavender, Lavandula angustifolia, oil on European seabass growth performance, innate immunity, antioxidant status, and organ histomorphometry.
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Abdel-Rahim, Mohamed M., Elhetawy, Ashraf. I. G., Mansour, Abdallah Tageldein, Mohamed, Radi A., Lotfy, Ayman M., Sallam, Ahmed E., and Shahin, Shimaa A.
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OXIDANT status , *EUROPEAN seabass , *DIETARY supplements , *NATURAL immunity , *HISTOMORPHOMETRY , *MORPHOMETRICS , *DIGESTIVE enzymes - Abstract
A long-term feeding trial (90 days) was conducted to investigate the effects of dietary supplementation with lavender oil (LO) on the growth performance, innate immunity, antioxidant status, and histomorphometry of different organs of juvenile European seabass (Dicentrarchus labrax). Four groups in triplicate were fed increasing levels of LO (0, 1, 2, and 3 kg−1 diet, expressed as F0, F1, F2, and F3, respectively). Fish weighing 76.87 ± 0.14 g/fish were stocked in 1000-L tanks at an initial stocking density of 25 fish. The results revealed that growth performance and feed utilization indices were significantly improved in the LO-treated groups compared to the control, with the highest values in favor of the F2 group. According to the polynomial second-order regression, the optimal dietary level of LO averaged 2.15–2.24 g/kg diet. Whole body protein and digestive enzyme activities were increased with increasing LO supplementation levels up to 2 mL kg−1. Fish-fed F2 diet exhibited a significant decrease in serum liver function enzymes. A considerable increase in total protein, albumin, and total immunoglobulin was reported in LO-supplemented groups over the control. Dietary LO significantly modulated antioxidant status by increasing antioxidant enzyme activities and decreasing malondialdehyde levels. Microscopic investigation of the gills, liver, and mid-intestine revealed that LO-treated fish had healthier histological features, with normal gill lamella and hepatocytes, and a positive effect of LO on intestinal villi length and goblet cell count. The LO could be used as a dietary supplement in the diet of seabass at the recommended level of 2 g kg−1 to improve growth, feed conversion, physiological status, and organ histomorphometry. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Fumarate hydratase as a metabolic regulator of immunity.
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Peace, Christian G., O'Carroll, Shane M., and O'Neill, Luke A.J.
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KREBS cycle , *SYSTEMIC lupus erythematosus , *THERAPEUTICS , *RENAL cancer , *CELL physiology , *TYPE I interferons , *NUCLEIC acids , *PLANT mitochondria - Abstract
Metabolism is a key regulator of immune cell function. Tricarboxylic acid cycle rewiring and metabolites have immunoregulatory roles. Fumarate hydratase (FH) and fumarate are now known to regulate cytokine production. Recent findings suggest FH loss leads to mitochondrial nucleic acid release, leading to type I interferon production. Tricarboxylic acid (TCA) cycle metabolites have been implicated in modulating signalling pathways in immune cells. Notable examples include succinate and itaconate, which have pro- and anti-inflammatory roles, respectively. Recently, fumarate has emerged as having specific roles in macrophage activation, regulating the production of such cytokines as interleukin (IL)-10 and type I interferons (IFNs). Fumarate hydratase (FH) has been identified as a control point. Notably, FH loss in different models and cell types has been found to lead to DNA and RNA release from mitochondria which are sensed by cytosolic nucleic acid sensors including retinoic acid-inducible gene (RIG)-I, melanoma differentiation-associated protein (MDA)5, and cyclic GMP-AMP synthase (cGAS) to upregulate IFN-β production. These findings may have relevance in the pathogenesis and treatment of diseases associated with decreased FH levels such as systemic lupus erythematosus (SLE) or FH-deficient kidney cancer. Tricarboxylic acid (TCA) cycle metabolites have been implicated in modulating signalling pathways in immune cells. Notable examples include succinate and itaconate, which have pro- and anti-inflammatory roles respectively. Recently, fumarate has emerged as having specific roles in macrophage activation, regulating the production of such cytokines as interleukin (IL)-10 and type I interferons (IFNs). Fumarate hydratase (FH) has been identified as a control point. Notably, FH loss in different models and cell types has been found to lead to DNA and RNA release from mitochondria which are sensed by cytosolic nucleic acid sensors including retinoic acid-inducible gene (RIG)-I, melanoma differentiation-associated protein (MDA)5, and cyclic GMP-AMP synthase (cGAS) to upregulate IFN-β production. These findings may have relevance in the pathogenesis and treatment of diseases associated with decreased FH levels such as systemic lupus erythematosus or FH-deficient kidney cancer. [ABSTRACT FROM AUTHOR]
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- 2024
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19. The contribution of the meningeal immune interface to neuroinflammation in traumatic brain injury.
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Mokbel, Alaa Y., Burns, Mark P., and Main, Bevan S.
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BRAIN injuries , *NEUROINFLAMMATION , *ALZHEIMER'S disease , *LYMPHATICS , *NEUROLOGICAL disorders , *BULLOUS pemphigoid - Abstract
Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide, particularly among the elderly, yet our mechanistic understanding of what renders the post-traumatic brain vulnerable to poor outcomes, and susceptible to neurological disease, is incomplete. It is well established that dysregulated and sustained immune responses elicit negative consequences after TBI; however, our understanding of the neuroimmune interface that facilitates crosstalk between central and peripheral immune reservoirs is in its infancy. The meninges serve as the interface between the brain and the immune system, facilitating important bi-directional roles in both healthy and disease settings. It has been previously shown that disruption of this system exacerbates neuroinflammation in age-related neurodegenerative disorders such as Alzheimer's disease; however, we have an incomplete understanding of how the meningeal compartment influences immune responses after TBI. In this manuscript, we will offer a detailed overview of the holistic nature of neuroinflammatory responses in TBI, including hallmark features observed across clinical and animal models. We will highlight the structure and function of the meningeal lymphatic system, including its role in immuno-surveillance and immune responses within the meninges and the brain. We will provide a comprehensive update on our current knowledge of meningeal-derived responses across the spectrum of TBI, and identify new avenues for neuroimmune modulation within the neurotrauma field. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Decoding Behcet's Uveitis: an In-depth review of pathogenesis and therapeutic advances.
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Guan, Yuxuan, Li, Fuzhen, Li, Na, and Yang, Peizeng
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BEHCET'S disease , *IRIDOCYCLITIS , *UVEITIS , *PATHOGENESIS , *NATURAL immunity , *REGULATORY T cells - Abstract
Behcet's disease (BD) is a rare but globally distributed vasculitis that primarily affects populations in the Mediterranean and Asian regions. Behcet's uveitis (BU) is a common manifestation of BD, occurring in over two-thirds of the patients. BU is characterized by bilateral, chronic, recurrent, non-granulomatous uveitis in association with complications such as retinal ischemia and atrophy, optic atrophy, macular ischemia, macular edema, and further neovascular complications (vitreous hemorrhage, neovascular glaucoma). Although the etiology and pathogenesis of BU remain unclear, numerous studies reveal that genetic factors (such as HLA-B51), dysregulated immune responses of both the innate and adaptive immune systems, infections (such as streptococcus), and environmental factors (such as GDP) are all involved in its development. Innate immunity, including hyperactivity of neutrophils and γδT cells and elevated NK1/NK2 ratios, has been shown to play an essential role in this disease. Adaptive immune system disturbance, including homeostatic perturbations, Th1, Th17 overaction, and Treg cell dysfunction, is thought to be involved in BU pathogenesis. Treatment of BU requires a tailored approach based on the location, severity of inflammation, and systemic manifestations. The therapy aims to achieve rapid inflammation suppression, preservation of vision, and prevention of recurrence. Systemic corticosteroids combined with other immunosuppressive agents have been widely used to treat BU, and beneficial effects are observed in most patients. Recently, biologics have been shown to be effective in treating refractory BU cases. Novel therapeutic targets for treating BU include the LCK gene, Th17/Treg balance, JAK pathway inhibition, and cytokines such as IL-17 and RORγt. This article summarizes the recent studies on BU, especially in terms of pathogenesis, diagnostic criteria and classification, auxiliary examination, and treatment options. A better understanding of the significance of microbiome composition, genetic basis, and persistent immune mechanisms, as well as advancements in identifying new biomarkers and implementing objective quantitative detection of BU, may greatly contribute to improving the adequate management of BU patients. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Introduction of sugar-modified nucleotides into CpG-containing antisense oligonucleotides inhibits TLR9 activation.
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Yoshida, Tokuyuki, Hagihara, Tomoko, Uchida, Yasunori, Horiuchi, Yoshiyuki, Sasaki, Kiyomi, Yamamoto, Takenori, Yamashita, Takuma, Goda, Yukihiro, Saito, Yoshiro, Yamaguchi, Takao, Obika, Satoshi, Yamamoto, Seiji, and Inoue, Takao
- Abstract
Antisense oligonucleotides (ASOs) are synthetic single-stranded oligonucleotides that bind to RNAs through Watson–Crick base pairings. They are actively being developed as therapeutics for various human diseases. ASOs containing unmethylated deoxycytidylyl-deoxyguanosine dinucleotide (CpG) motifs are known to trigger innate immune responses via interaction with toll-like receptor 9 (TLR9). However, the TLR9-stimulatory properties of ASOs, specifically those with lengths equal to or less than 20 nucleotides, phosphorothioate linkages, and the presence and arrangement of sugar-modified nucleotides—crucial elements for ASO therapeutics under development—have not been thoroughly investigated. In this study, we first established SY-ODN18, an 18-nucleotide phosphorothioate oligodeoxynucleotide with sufficient TLR9-stimulatory activity. We demonstrated that an unmethylated CpG motif near its 5′-end was indispensable for TLR9 activation. Moreover, by utilizing various sugar-modified nucleotides, we systematically generated model ASOs, including gapmer, mixmer, and fully modified designs, in accordance with the structures of ASO therapeutics. Our results illustrated that introducing sugar-modified nucleotides in such designs significantly reduces TLR9-stimulatory activity, even without methylation of CpG motifs. These findings would be useful for drug designs on several types of ASOs. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Neutrophil Virucidal Activity Against SARS-CoV-2 Is Mediated by Neutrophil Extracellular Traps.
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Almeida, Cícero José Luíz dos Ramos, Veras, Flávio Protásio, Paiva, Isadora Marques, Schneider, Ayda Henriques, Silva, Juliana da Costa, Gomes, Giovanni Freitas, Costa, Victor Ferreira, Silva, Bruna Manuella Souza, Caetite, Diego Brito, Silva, Camila Meirelles Souza, Salina, Ana Caroline Guerta, Martins, Ronaldo, Bonilha, Caio Santos, Cunha, Larissa Dias, Jamur, Maria Célia, Silva, Luís Lamberti Pinto da, Arruda, Eurico, Zamboni, Dario Simões, Louzada-Junior, Paulo, and Oliveira, Renê Donizeti Ribeiro de
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COVID-19 , *LEUCOCYTE elastase , *SARS-CoV-2 , *NEUTROPHILS , *EPITHELIAL cells - Abstract
Background Inflammation in the lungs and other vital organs in COVID-19 is characterized by the presence of neutrophils and a high concentration of neutrophil extracellular traps (NETs), which seems to mediate host tissue damage. However, it is not known whether NETs could have virucidal activity against SARS-CoV-2. Methods We investigated whether NETs could prevent SARS-CoV-2 replication in neutrophils and epithelial cells and what the consequence of NETs degradation would be in K18-humanized ACE2 transgenic mice infected with SARS-CoV-2. Results Here, by immunofluorescence microscopy, we observed that viral particles colocalize with NETs in neutrophils isolated from patients with COVID-19 or healthy individuals and infected in vitro. The inhibition of NETs production increased virus replication in neutrophils. In parallel, we observed that NETs inhibited virus abilities to infect and replicate in epithelial cells after 24 hours of infection. Degradation of NETs with DNase I prevented their virucidal effect in vitro. Using K18-humanized ACE2 transgenic mice, we observed a higher viral load in animals treated with DNase I. However, the virucidal effect of NETs was not dependent on neutrophil elastase or myeloperoxidase activity. Conclusions Our results provide evidence of the role of NETosis as a mechanism of SARS-CoV-2 viral capture and inhibition. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Peptides with Antimicrobial Activity in the Saliva of the Malaria Vector Anopheles coluzzii.
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Bevivino, Giulia, Maurizi, Linda, Ammendolia, Maria Grazia, Longhi, Catia, Arcà, Bruno, and Lombardo, Fabrizio
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ANTIMICROBIAL peptides , *ANOPHELES , *AMINO acid residues , *SALIVA , *ESCHERICHIA coli , *GRAM-positive bacteria , *STAPHYLOCOCCUS aureus - Abstract
Mosquito saliva plays a crucial physiological role in both sugar and blood feeding by helping sugar digestion and exerting antihemostatic functions. During meal acquisition, mosquitoes are exposed to the internalization of external microbes. Since mosquitoes reingest significant amounts of saliva during feeding, we hypothesized that salivary antimicrobial components may participate in the protection of mouthparts, the crop, and the gut by inhibiting bacterial growth. To identify novel potential antimicrobials from mosquito saliva, we selected 11 candidates from Anopheles coluzzii salivary transcriptomic datasets and obtained them either using a cell-free transcription/translation expression system or, when feasible, via chemical synthesis. Hyp6.2 and hyp13, which were predicted to be produced as propeptides and cleaved in shorter mature forms, showed the most interesting results in bacterial growth inhibition assays. Hyp6.2 (putative mature form, 35 amino acid residues) significantly inhibited the growth of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Serratia marcescens) bacteria. Hyp13 (short form, 19 amino acid residues) dose-dependently inhibited E. coli and S. marcescens growth, inducing membrane disruption in both Gram-positive and Gram-negative bacteria as indicated with scanning electron microscopy. In conclusion, we identified two A. coluzzii salivary peptides inhibiting Gram-positive and Gram-negative bacteria growth and possibly contributing to the protection of mosquito mouthparts and digestive tracts from microbial infection during and/or after feeding. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Nucleotide-Binding Oligomerization Domain 1 (NOD1) Agonists Prevent SARS-CoV-2 Infection in Human Lung Epithelial Cells through Harnessing the Innate Immune Response.
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Garcia-Vidal, Edurne, Calba, Ignasi, Riveira-Muñoz, Eva, García, Elisabet, Clotet, Bonaventura, Serra-Mitjà, Pere, Cabrera, Cecilia, Ballana, Ester, and Badia, Roger
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LUNGS , *SARS-CoV-2 , *EPITHELIAL cells , *LUNG infections , *PATTERN perception receptors , *IMMUNE response - Abstract
The lung is prone to infections from respiratory viruses such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). A challenge in combating these infections is the difficulty in targeting antiviral activity directly at the lung mucosal tract. Boosting the capability of the respiratory mucosa to trigger a potent immune response at the onset of infection could serve as a potential strategy for managing respiratory infections. This study focused on screening immunomodulators to enhance innate immune response in lung epithelial and immune cell models. Through testing various subfamilies and pathways of pattern recognition receptors (PRRs), the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family was found to selectively activate innate immunity in lung epithelial cells. Activation of NOD1 and dual NOD1/2 by the agonists TriDAP and M-TriDAP, respectively, increased the number of IL-8+ cells by engaging the NF-κB and interferon response pathways. Lung epithelial cells showed a stronger response to NOD1 and dual NOD1/2 agonists compared to control. Interestingly, a less-pronounced response to NOD1 agonists was noted in PBMCs, indicating a tissue-specific effect of NOD1 in lung epithelial cells without inducing widespread systemic activation. The specificity of the NOD agonist pathway was confirmed through gene silencing of NOD1 (siRNA) and selective NOD1 and dual NOD1/2 inhibitors in lung epithelial cells. Ultimately, activation induced by NOD1 and dual NOD1/2 agonists created an antiviral environment that hindered SARS-CoV-2 replication in vitro in lung epithelial cells. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Gut Microbiota as a Modifier of Huntington’s Disease Pathogenesis.
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Khoshnan, Ali
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Huntingtin (HTT) protein is expressed in most cell lineages, and the toxicity of mutant HTT in multiple organs may contribute to the neurological and psychiatric symptoms observed in Huntington’s disease (HD). The proteostasis and neurotoxicity of mutant HTT are influenced by the intracellular milieu and responses to environmental signals. Recent research has highlighted a prominent role of gut microbiota in brain and immune system development, aging, and the progression of neurological disorders. Several studies suggest that mutant HTT might disrupt the homeostasis of gut microbiota (known as dysbiosis) and impact the pathogenesis of HD. Dysbiosis has been observed in HD patients, and in animal models of the disease it coincides with mutant HTT aggregation, abnormal behaviors, and reduced lifespan. This review article aims to highlight the potential toxicity of mutant HTT in organs and pathways within the microbiota-gut-immune-central nervous system (CNS) axis. Understanding the functions of Wild-Type (WT) HTT and the toxicity of mutant HTT in these organs and the associated networks may elucidate novel pathogenic pathways, identify biomarkers and peripheral therapeutic targets for HD. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Evolutionary immunology to explore original antiviral strategies.
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Imler, Jean-Luc, Cai, Hua, Meignin, Carine, and Martins, Nelson
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HOMEOBOX genes , *DEVELOPMENTAL biology , *EVOLUTIONARY developmental biology , *ANIMAL diversity , *COLONIZATION (Ecology) , *IMMUNOLOGY - Abstract
Over the past 25 years, the field of evolutionary developmental biology (evo–devo) has used genomics and genetics to gain insight on the developmental mechanisms underlying the evolution of morphological diversity of animals. Evo–devo exploits the key insight that conserved toolkits of development (e.g. Hox genes) are used in animals to produce genetic novelties that provide adaptation to a new environment. Like development, immunity is forged by interactions with the environment, namely the microbial world. Yet, when it comes to the study of immune defence mechanisms in invertebrates, interest primarily focuses on evolutionarily conserved molecules also present in humans. Here, focusing on antiviral immunity, we argue that immune genes not conserved in humans represent an unexplored resource for the discovery of new antiviral strategies. We review recent findings on the cGAS-STING pathway and explain how cyclic dinucleotides produced by cGAS-like receptors may be used to investigate the portfolio of antiviral genes in a broad range of species. This will set the stage for evo–immuno approaches, exploiting the investment in antiviral defences made by metazoans over hundreds of millions of years of evolution. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'. [ABSTRACT FROM AUTHOR]
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- 2024
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27. Innate immunity in Aedes mosquitoes: from pathogen resistance to shaping the microbiota.
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Hixson, Bretta, Chen, Robin, and Buchon, Nicolas
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AEDES aegypti , *AEDES , *ARBOVIRUSES , *INSECT physiology , *NATURAL immunity , *PLASMODIUM , *MOSQUITOES , *ANTIMICROBIAL peptides , *IMMUNOMODULATORS - Abstract
Discussions of host–microbe interactions in mosquito vectors are frequently dominated by a focus on the human pathogens they transmit (e.g. Plasmodium parasites and arboviruses). Underlying the interactions between a vector and its transmissible pathogens, however, is the physiology of an insect living and interacting with a world of bacteria and fungi including commensals, mutualists and primary and opportunistic pathogens. Here we review what is known about the bacteria and fungi associated with mosquitoes, with an emphasis on the members of the Aedes genus. We explore the reciprocal effects of microbe on mosquito, and mosquito on microbe. We analyse the roles of bacterial and fungal symbionts in mosquito development, their effects on vector competence, and their potential uses as biocontrol agents and vectors for paratransgenesis. We explore the compartments of the mosquito gut, uncovering the regionalization of immune effectors and modulators, which create the zones of resistance and immune tolerance with which the mosquito host controls and corrals its microbial symbionts. We examine the anatomical patterning of basally expressed antimicrobial peptides. Finally, we review the relationships between inducible antimicrobial peptides and canonical immune signalling pathways, comparing and contrasting current knowledge on each pathway in mosquitoes to the model insect Drosophila melanogaster. This article is part of the theme issue 'Sculpting the microbiome: how host factors determine and respond to microbial colonization'. [ABSTRACT FROM AUTHOR]
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- 2024
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28. The emerging roles of glutamine amidotransferases in metabolism and immune defense.
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Xie, Taolin, Qin, Chao, Savas, Ali Can, Yeh, Wayne Wei, and Feng, Pinghui
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AbstractGlutamine amidotransferases (GATs) catalyze the synthesis of nucleotides, amino acids, glycoproteins and an enzyme cofactor, thus serving as key metabolic enzymes for cell proliferation.
C arbamoyl-phosphate synthetase,A spartate transcarbamoylase, andD ihydroorotase (CAD) is a multifunctional enzyme of the GAT family and catalyzes the first three steps of thede novo pyrimidine synthesis. Following our findings that cellular GATs are involved in immune evasion during herpesvirus infection, we discovered that CAD reprograms cellular metabolism to fuel aerobic glycolysis and nucleotide synthesisvia deamidating RelA. Deamidated RelA activates the expression of key glycolytic enzymes, rather than that of the inflammatory NF-κB-responsive genes. As such, cancer cells prime RelA for deamidationvia up-regulating CAD activity or accumulating RelA mutations. Interestingly, the recently emerged SARS-CoV-2 also activates CAD to couple evasion of inflammatory response to activated nucleotide synthesis. A small molecule inhibitor of CAD depletes nucleotide supply and boosts antiviral inflammatory response, thus greatly reducing SARS-CoV-2 replication. Additionally, we also found that CTP synthase 1 (CTPS1) deamidates interferon (IFN) regulatory factor 3 (IRF3) to mute IFN induction. Our previous studies have implicated phosphoribosyl formylglycinamidine synthase (PFAS) and phosphoribosyl pyrophosphate amidotransferase (PPAT) in deamidating retinoic acid-inducible gene I (RIG-I) and evading dsRNA-induced innate immune defense in herpesvirus infection. Overall, these studies have uncovered an unconventional enzymatic activity of cellular GATs in metabolism and immune defense, offering a molecular link intimately coupling these fundamental biological processes. [ABSTRACT FROM AUTHOR]- Published
- 2024
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29. Optimizing cryopreservation of nasal polyp tissue for cellular functional studies and single-cell RNA sequencing.
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Sohail, Aaqib, Baloh, Carolyn H., Hacker, Jonathan, Cho, Laura, Ryan, Tessa, Bergmark, Regan W., Lee, Stella E., Maxfield, Alice, Roditi, Rachel, Dwyer, Daniel F., Buchheit, Kathleen M., and Laidlaw, Tanya M.
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CRYOPRESERVATION of cells , *NASAL polyps , *RNA sequencing , *PLASMA cells , *PARANASAL sinus diseases , *TISSUES - Abstract
This research note explores the optimization of cryopreservation methods for nasal polyp tissue to enable cellular functional studies and single-cell RNA sequencing. The study compares different cryopreservation methods and assesses their impact on cell viability, immune cell subset composition, and gene expression profiles. The findings suggest that the choice of cryopreservation method should be tailored to the specific goals and cell types of the research project. The study aims to enhance methodology for future clinical trials and tissue biobanks. The article also provides information on quality control parameters and the mast cell transcriptome. The authors disclose no conflicts of interest. [Extracted from the article]
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- 2024
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30. Recent advances in potential targets for myocardial ischemia reperfusion injury: Role of macrophages.
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Zhuang, Qigang, Li, Mingyue, Hu, Desheng, and Li, Junyi
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MYOCARDIAL reperfusion , *REPERFUSION injury , *MYOCARDIAL ischemia , *MACROPHAGES , *MYOCARDIAL infarction , *TOLL-like receptors - Abstract
Myocardial ischemia-reperfusion injury (MIRI) is a complex process that occurs when blood flow is restored after myocardium infarction (MI) with exacerbated tissue damage. Macrophages, essential cell type of the immune response, play an important role in MIRI. Macrophage subpopulations, namely M1 and M2, are distinguished by distinct phenotypes and functions. In MIRI, macrophages infiltrate in infarcted area, shaping the inflammatory response and influencing tissue healing. Resident cardiac macrophages interact with monocyte-derived macrophages in MIRI, and influence injury progression. Key factors including chemokines, cytokines, and toll-like receptors modulate macrophage behavior in MIRI. This review aims to address recent findings on the classification and the roles of macrophages in the myocardium, spanning from MI to subsequent MIRI, and highlights various signaling pathways implicated in macrophage polarization underlining the complexity of MIRI. This article will shed light on developing advanced therapeutic strategies for MIRI management. • Modulation of macrophage polarization as a potential target for treating Myocardial Ischemia Reperfusion Injury (MIRI). • Summary for cell types of macrophages and their function. • Localization & phenotypes of macrophages in myocardial tissue. • Conclusion for recent researches of the potential mechanism of macrophages during myocardial infarction (MI) & MIRI. [ABSTRACT FROM AUTHOR]
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- 2024
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31. The Dynamic Relationship between Dengue Virus and the Human Cutaneous Innate Immune Response.
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Martí, Michelle M., Castanha, Priscila M. S., and Barratt-Boyes, Simon M.
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DENGUE viruses , *IMMUNE response , *PATTERN perception receptors , *LANGERHANS cells , *CYTOKINE receptors , *ARTHROPOD vectors , *MAST cells - Abstract
Dengue virus (DENV) is a continuing global threat that puts half of the world's population at risk for infection. This mosquito-transmitted virus is endemic in over 100 countries. When a mosquito takes a bloodmeal, virus is deposited into the epidermal and dermal layers of human skin, infecting a variety of permissive cells, including keratinocytes, Langerhans cells, macrophages, dermal dendritic cells, fibroblasts, and mast cells. In response to infection, the skin deploys an array of defense mechanisms to inhibit viral replication and prevent dissemination. Antimicrobial peptides, pattern recognition receptors, and cytokines induce a signaling cascade to increase transcription and translation of pro-inflammatory and antiviral genes. Paradoxically, this inflammatory environment recruits skin-resident mononuclear cells that become infected and migrate out of the skin, spreading virus throughout the host. The details of the viral–host interactions in the cutaneous microenvironment remain unclear, partly due to the limited body of research focusing on DENV in human skin. This review will summarize the functional role of human skin, the cutaneous innate immune response to DENV, the contribution of the arthropod vector, and the models used to study DENV interactions in the cutaneous environment. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Nuclear-targeted chimeric peptide nanorods to amplify innate anti-tumor immunity through localized DNA damage and STING activation.
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Wu, Yeyang, Li, Yanmei, Yan, Ni, Huang, Jiaqi, Li, Xinyu, Zhang, Keyan, Lu, Zhenming, Qiu, Ziwen, and Cheng, Hong
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NATURAL immunity , *PEPTIDES , *KILLER cells , *DNA damage , *CYTOTOXIC T cells , *NANOMEDICINE - Abstract
Stimulator of the interferon genes (STING) pathway is appealing but challenging to potentiate the innate anti-tumor immunity. In this work, nuclear-targeted chimeric peptide nanorods (designated as PFPD) are constructed to amplify innate immunity through localized DNA damage and STING activation. Among which, the chimeric peptide (PpIX-FFVLKPKKKRKV) is fabricated with photosensitizer and nucleus targeting peptide sequence, which can self-assemble into nanorods and load STING agonist of DMXAA. The uniform nanosize distribution and good stability of PFPD improve the sequential targeting delivery of drugs towards tumor cells and nuclei. Under light irradiation, PFPD produce a large amount of reactive oxygen species (ROS) to destroy nuclear DNA in situ , and the released cytosolic DNA fragment will efficiently activate innate anti-tumor immunity in combination with STING agonist. In vitro and in vivo results indicate the superior ability of PFPD to activate natural killer cells and T cells, thus efficiently eradicating lung metastatic tumor without inducing unwanted side effects. This work provides a sophisticated strategy for localized activation of innate immunity for systemic tumor treatment, which may inspire the rational design of nanomedicine for tumor precision therapy. A nuclear-targeted chimeric peptide is constructed to load STING agonist developing stable and uniform nanorods. The nanorods upon light excitation can generate reactive oxygen species (ROS) to destroy nuclear DNA in situ , and the released cytosolic DNA fragments will efficiently activate innate anti-tumor immunity in combination with STING agonist, thus enhancing the suppression on tumor proliferation and metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]
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- 2024
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33. Genome‐wide association studies for diarrhoea outcomes identified genomic regions affecting resistance to a severe enteropathy in suckling rabbits.
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Bovo, Samuele, Ribani, Anisa, Schiavo, Giuseppina, Taurisano, Valeria, Bertolini, Francesca, Fornasini, Daniela, Frabetti, Andrea, and Fontanesi, Luca
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GENOME-wide association studies , *INTESTINAL diseases , *RABBITS , *DIARRHEA , *HERITABILITY , *IMMUNOGLOBULIN receptors - Abstract
Selection and breeding strategies to improve resistance to enteropathies are essential to reaching the sustainability of the rabbit production systems. However, disease heterogeneity (having only as major visible symptom diarrhoea) and low disease heritability are two barriers for the implementation of these strategies. Diarrhoea condition can affect rabbits at different life stages, starting from the suckling period, with large negative economic impacts. In this study, from a commercial population of suckling rabbits (derived from 133 litters) that experienced an outbreak of enteropathy, we first selected a few animals that died with severe symptoms of diarrhoea and characterized their microbiota, using 16S rRNA gene sequencing data. Clostridium genus was consistently present in all affected specimens. In addition, with the aim to identify genetic markers in the rabbit genome that could be used as selection tools, we performed genome‐wide association studies for symptoms of diarrhoea in the same commercial rabbit population. These studies were also complemented with FST analyses between the same groups of rabbits. A total of 332 suckling rabbits (151 with severe symptoms of diarrhoea, 42 with mild symptoms and 129 without any symptoms till the weaning period), derived from 45 different litters (a subset of the 133 litters) were genotyped with the Affymetrix Axiom OrcunSNP Array. In both genomic approaches, rabbits within litters were paired to constitute two groups (susceptible and resistant, including the mildly affected in one or the other group) and run case and control genome‐wide association analyses. Genomic heritability estimated in the designed experimental structure integrated in a commercial breeding scheme was 0.19–0.21 (s.e. 0.09–0.10). A total of eight genomic regions on rabbit chromosome 2 (OCU2), OCU3, OCU7, OCU12, OCU13, OCU16 and in an unassembled scaffold had significant single nucleotide polymorphisms (SNPs) and/or markers that trespassed the FST percentile distribution. Among these regions, three main peaks of SNPs were identified on OCU12, OCU13 and OCU16. The QTL region on OCU13 encompasses several genes that encode members of a family of immunoglobulin Fc receptors (FCER1G, FCRLA, FCRLB and FCGR2A) involved in the immune innate system, which might be important candidate genes for this pathogenic condition. The results obtained in this study demonstrated that resistance to an enteropathy occurring in suckling rabbits is in part genetically determined and can be dissected at the genomic level, providing DNA markers that could be used in breeding programmes to increase resistance to enteropathies in meat rabbits. [ABSTRACT FROM AUTHOR]
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- 2024
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34. Unraveling the Complexities of Toll-like Receptors: From Molecular Mechanisms to Clinical Applications.
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Chen, Yi-Hsin, Wu, Kang-Hsi, and Wu, Han-Ping
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TOLL-like receptors , *CLINICAL medicine , *MEDICAL research , *VACCINE development , *IMMUNE system , *COMPUTATIONAL neuroscience - Abstract
Toll-like receptors (TLRs) are vital components of the innate immune system, serving as the first line of defense against pathogens by recognizing a wide array of molecular patterns. This review summarizes the critical roles of TLRs in immune surveillance and disease pathogenesis, focusing on their structure, signaling pathways, and implications in various disorders. We discuss the molecular intricacies of TLRs, including their ligand specificity, signaling cascades, and the functional consequences of their activation. The involvement of TLRs in infectious diseases, autoimmunity, chronic inflammation, and cancer is explored, highlighting their potential as therapeutic targets. We also examine recent advancements in TLR research, such as the development of specific agonists and antagonists, and their application in immunotherapy and vaccine development. Furthermore, we address the challenges and controversies surrounding TLR research and outline future directions, including the integration of computational modeling and personalized medicine approaches. In conclusion, TLRs represent a promising frontier in medical research, with the potential to significantly impact the development of novel therapeutic strategies for a wide range of diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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35. Potential Involvement of the South American Lungfish Intelectin-2 in Innate-Associated Immune Modulation.
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Bernardes, Gabriela Patrícia Martins de Almeida, Serra, Gustavo Marques, Silva, Lucas da Silva e, Martins, Maíra Pompeu, Perez, Louise Neiva, Molfetta, Fábio Alberto de, Santos, Agenor Valadares, and Schneider, Maria Paula Cruz
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QUATERNARY structure , *IMMUNOREGULATION , *MOLECULAR docking , *DISACCHARIDES , *MOLECULAR weights , *MALTOSE , *LECTINS , *GLOBULAR proteins - Abstract
Intelectins belong to a family of lectins with specific and transitory carbohydrate interaction capabilities. These interactions are related to the activity of agglutinating pathogens, as intelectins play a significant role in immunity. Despite the prominent immune defense function of intelectins, limited information about its structural characteristics and carbohydrate interaction properties is available. This study investigated an intelectin transcript identified in RNA-seq data obtained from the South American lungfish (Lepidosiren paradoxa), namely LpITLN2-B. The structural analyses predicted LpITLN2-B to be a homo-trimeric globular protein with the fibrinogen-like functional domain (FReD), exhibiting a molecular mass of 57 kDa. The quaternary structure is subdivided into three monomers, A, B, and C, and each domain comprises 11 β-sheets: an anti-parallel β-sheet, a β-hairpin, and a disordered β-sheet structure. Molecular docking demonstrates a significant interaction with disaccharides rather than monosaccharides. The preferential interaction with disaccharides highlights the potential interaction with pathogen molecules, such as LPS and Poly(I:C). The hemagglutination assay inhibited lectins activity, especially maltose and sucrose, highlighting lectin activity in L. paradoxa samples. Overall, our results show the potential relevance of LpITLN2-B in L. paradoxa immune defense against pathogens. [ABSTRACT FROM AUTHOR]
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- 2024
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36. Herpes Simplex Virus ICP27 Protein Inhibits AIM 2-Dependent Inflammasome Influencing Pro-Inflammatory Cytokines Release in Human Pigment Epithelial Cells (hTert-RPE 1).
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Caproni, Anna, Nordi, Chiara, Fontana, Riccardo, Facchini, Martina, Melija, Sara, Pappadà, Mariangela, Buratto, Mattia, and Marconi, Peggy
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HERPES simplex virus , *HUMAN herpesvirus 1 , *CHROMATOPHORES , *VIRAL proteins , *INFLAMMASOMES - Abstract
Although Herpes simplex virus type 1 (HSV-1) has been deeply studied, significant gaps remain in the fundamental understanding of HSV-host interactions: our work focused on studying the Infected Cell Protein 27 (ICP27) as an inhibitor of the Absent-in-melanoma-2 (AIM 2) inflammasome pathway, leading to reduced pro-inflammatory cytokines that influence the activation of a protective innate immune response to infection. To assess the inhibition of the inflammasome by the ICP27, hTert-immortalized Retinal Pigment Epithelial cells (hTert-RPE 1) infected with HSV-1 wild type were compared to HSV-1 lacking functional ICP27 (HSV-1∆ICP27) infected cells. The activation of the inflammasome by HSV-1∆ICP27 was demonstrated by quantifying the gene and protein expression of the inflammasome constituents using real-time PCR and Western blot. The detection of the cleavage of the pro-caspase-1 into the active form was performed by using a bioluminescent assay, while the quantification of interleukins 1β (IL-1β) and 18 (IL-18)released in the supernatant was quantified using an ELISA assay. The data showed that the presence of the ICP27 expressed by HSV-1 induces, in contrast to HSV-1∆ICP27 vector, a significant downregulation of AIM 2 inflammasome constituent proteins and, consequently, the release of pro-inflammatory interleukins into the extracellular environment reducing an effective response in counteracting infection. [ABSTRACT FROM AUTHOR]
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- 2024
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37. Enduring echoes: Post-infectious long-term changes in innate immunity.
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Dulfer, Elisabeth A., Joosten, Leo A.B., and Netea, Mihai G.
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NATURAL immunity , *POST-infectious disorders , *IMMUNE response , *IMMUNOSUPPRESSION , *CARDIOLOGICAL manifestations of general diseases - Abstract
• Memory-like features can be induced in innate immune cells after pathogen exposure. • Trained immunity may be involved in the pathophysiology of post-infectious clinical syndromes. • Hyperinflammation or post-infectious immune paralysis are targets for treatment. Upon encountering pathogens, the immune system typically responds by initiating an acute and self-limiting reaction, with symptoms subsiding after the pathogen has been cleared. However, long-term post-infectious clinical symptoms can manifest months or even years after the initial infection. 'Trained immunity', the functional reprogramming of innate immune cells through epigenetic and metabolic rewiring, has been proposed as a key concept for understanding these long-term effects. Although trained immunity can result in enhanced protection against reinfection with heterologous pathogens, it can also contribute to detrimental outcomes. Persisting and excessive inflammation can cause tissue damage and aggravate immune-mediated conditions and cardiovascular complications. On the other hand, suppression of immune cell effector functions by long-lasting epigenetic changes can result in post-infectious immune paralysis. Distinct stimuli can evoke different trained immunity programs, potentially resulting in different consequences for the host. In this review, we provide an overview of both the adaptive and maladaptive consequences of infectious diseases. We discuss how long-term immune dysregulation in patients can be addressed by tailoring host-directed interventions and identify areas of scientific and therapeutic potential to advance further. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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38. Dietary Tryptophan Plays a Role as an Anti-Inflammatory Agent in European Seabass (Dicentrarchus labrax) Juveniles during Chronic Inflammation.
- Author
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Azeredo, Rita, Peixoto, Diogo, Santos, Paulo, Duarte, Inês, Ricardo, Ana, Aragão, Cláudia, Machado, Marina, and Costas, Benjamín
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- *
EUROPEAN seabass , *FISH feeds , *TRYPTOPHAN , *ANTI-inflammatory agents , *DIETARY supplements , *INFLAMMATION - Abstract
Simple Summary: Where teleost fish are concerned, the effects of a dietary tryptophan surplus are mostly immunosuppressive, making it a potential dietary anti-inflammatory strategy. The goal of the present work was to evaluate the effects of tryptophan dietary supplementation on immune and neuroendocrine responses of the European seabass, Dicentrarchus labrax, undergoing chronic inflammation. Juvenile European seabass were intraperitoneally injected with an inflammatory agent (inflamed group) or a saline solution (control group). Within each group, fish were fed a control and a control-based diet supplemented with tryptophan for 4 weeks. Different tissues were sampled every week for the assessment of immune-related parameters. When tryptophan was provided to fish undergoing inflammation, the gene expression of a macrophage marker increased sooner and remained high until the end of the experiment. The same fish showed a concurrent increase in peripheral monocyte counts. After one week, molecular patterns of anti-inflammatory processes seemed to be favoured by tryptophan. Altogether, results show that a short administration period seems to be critical where tryptophan supplementation is concerned since at later inflammatory stages—and longer feeding periods—fish fed this diet displayed a molecular profile similar to that of fish fed a control diet. Where teleost fish are concerned, studies in tryptophan immunomodulation generally point to immunosuppressive properties, thus presenting a potential anti-inflammatory dietary strategy. The goal of the present work was to evaluate the effects of tryptophan dietary supplementation on immune and neuroendocrine responses of the European seabass, Dicentrarchus labrax, undergoing chronic inflammation. Juvenile European seabass were intraperitoneally injected with either Freund's Incomplete Adjuvant (FIA, inflamed group) or a saline solution (control group). Within each group, fish were fed a control (CTRL) and a CTRL-based diet supplemented with tryptophan (0.3% DM basis; TRP) for 4 weeks. Different tissues were sampled every week for the assessment of immune-related parameters. When TRP was provided to FIA-injected fish, mcsfr gene expression increased from 1 to 2 weeks and remained high until the end of the experiment. The same fish showed a concurrent increase in peripheral monocyte counts. Moreover, il34 expression at 1 week post-FIA injection was higher in TRP-fed than in CTRL-fed fish. After one week, molecular patterns of anti-inflammatory processes seemed to be favoured by TRP (mcsfr, gr1, il34 and tgfβ). Altogether, the results show that the feeding period seems to be critical where tryptophan supplementation is concerned since at later inflammatory stages—and longer feeding periods—fish fed TRP displayed a molecular profile similar to that of the CTRL group. In contrast, shorter administration periods might accelerate immune regulatory pathways. [ABSTRACT FROM AUTHOR]
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- 2024
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39. The role of IFN-γ-mediated host immune responses in monitoring and the elimination of Toxoplasma gondii infection.
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Ihara, Fumiaki and Yamamoto, Masahiro
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IMMUNE response , *TOXOPLASMA gondii , *KILLER cells , *CYTOTOXIC T cells , *PREGNANT women , *TRYPANOSOMA cruzi , *TRICHODERMA harzianum , *TRICHOMONIASIS - Abstract
Toxoplasma gondii is a pathogenic protozoan parasite of the Apicomplexa family that affects approximately 30% of the world's population. Symptoms are usually mild in immunocompetent hosts, but it can pose significant health risks to immunosuppressed patients and pregnant women. Current treatment options are limited, and new therapies and vaccines are needed. The innate immune system is the first to recognize T. gondii infection and activates pro-inflammatory cytokines and chemokines to promote acquired immunity. The IL-12/IFN-γ axis is particularly important, and when this pathway is inhibited, infection becomes uncontrolled and lethal. In mice, receptors such as Toll-like receptor 11 (TLR11), TLR12, and chemokine receptors are involved in T. gondii recognition and the modulation of immune responses. In humans, where TLR11 and TLR12 are absent, other mechanisms have been reported as the innate immune sensing system in T. gondii infection. Immune cells activated in response to infection produce interleukin (IL)-12, which stimulates the proliferation of natural killer cells and T cells and promotes the production of interferon (IFN)-γ. Several IFN-γ-induced anti- T. gondii defense mechanisms inhibit parasite growth. These include nitric oxide (NO) production, indoleamine 2,3-dioxygenase, and the destruction of parasitophorous vacuoles by IFN-γ-inducible immunity related GTPase groups (IRGs and GBPs). Recent studies focusing on the diversity of IRGs in rodents and effector molecules in T. gondii suggest that host immune mechanisms and pathogen immune evasion mechanisms have co-evolved. Furthermore, it has been suggested that cysts are not simply dormant during chronic infection. This review summarizes recent findings on anti- T. gondii innate, adaptive, and cell-autonomous immune responses. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Salicylic acid-doped iron nano-biostimulants potentiate defense responses and suppress Fusarium wilt in watermelon.
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Noman, Muhammad, Ahmed, Temoor, Shahid, Muhammad, Nazir, Muhammad Mudassir, Azizullah, Li, Dayong, and Song, Fengming
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- *
WATERMELONS , *FUSARIUM , *SUSTAINABILITY , *FUSARIUM oxysporum , *SALICYLIC acid , *FUNGAL growth - Abstract
[Display omitted] • Bio-FeNPs and SINCs supplement watermelon growth. • Soil drenching with bio-FeNPs and SINCs restrict invasive fungal growth. • Bio-FeNPs and SINCs modulate oxidative signaling in watermelon. • Bio-FeNPs and SINCs trigger defense responses in watermelon against Fusarium wilt. Chemo- and bio-genic metallic nanoparticles (NPs), as a novel nano-enabled strategy, have demonstrated a great potential in crop health management. The current study aimed to explore the efficacy of advanced nanocomposites (NCs), integrating biogenic (bio) metallic NPs and plant immunity-regulating hormones, in crop disease control. Iron (Fe) NPs were biosynthesized using cell-free supernatant of a Fe-resistant strains, Bacillus marisflavi ZJ-4. Further, salicylic acid-coated bio-FeNPs (SI) NCs were prepared via co-precipitation method under alkaline conditions. Both bio-FeNPs and SINCs were characterized using basic analytical techniques, including Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction analysis, and scanning/transmission electron microscopy. Bio-FeNPs and SINCs had variable shapes with average sizes of 72.35 nm and 65.87 nm, respectively. Under greenhouse conditions, bio-FeNPs and SINCs improved the agronomic traits of the watermelon plants, and SINCs outperformed bio-FeNPs, providing the maximum growth promotion of 32.5%. Soil-drenching with bio-FeNPs and SINCs suppressed Fusarium oxysporum f. sp. niveum -caused Fusarium wilt in watermelon, and SINCs provided better protection than bio-FeNPs, through inhibiting the fungal invasive growth within host plants. SINCs improved the antioxidative capacity and primed a systemic acquired resistance (SAR) response via activating the salicylic acid signaling pathway genes. These findings indicate that SINCs can reduce the severity of Fusarium wilt in watermelon by modulating antioxidative capacity and potentiating SAR to restrict in planta fungal invasive growth. This study provides new insights into the potential of bio-FeNPs and SINCs as biostimulants and bioprotectants for growth promotion and Fusarium wilt suppression, ensuring sustainable watermelon production. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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41. Testing androgen‐induced immunosuppression: Environmental androgens as a model system for steroid‐immune interaction.
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López‐Pérez, Jorge E., Goessling, Jeffrey M., and Murray, Christopher M.
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- *
ANDROGENS , *AMERICAN alligator , *ANTIBODY titer , *RATIO & proportion , *ENDOCRINE disruptors - Abstract
It is well known that hormones influence and direct most facets of physiology; however, there is still contention regarding the directions of certain relationships, for example, between gonadal hormones and immunity. Among the many proposed relationships relating to gonadal–immune interactions, support for immunosuppressive effects of androgens remains prominent within physiological literature. Although ample study has been directed toward the immunosuppressive effects of androgens, considerable disagreement remains regarding their influence on immune function. In this study, we test the hypothesis that androgens inhibit immunocompetence in the American alligator (Alligator mississippiensis). Developing alligators were incubated at female‐producing temperatures with a subset of individuals being exposed to 17‐α‐methyltestosterone (MT) before sexual determination. 17‐α‐methyltestosterone is a potent androgen, not aromatizable by crocodilians, that has been found to exert masculinizing effects in exposed crocodilian populations in vivo and in vitro. Additionally, a subset of animals was exposed to a novel antigen to quantify innate and acquired immune function. We recovered no significant differences in leukocyte ratios or proportions between groups and found no significant differences in innate immune function as measured by hemolysis‐hemagglutination. However, we did find significant differences in acquired immune function, where masculinized individuals expressed greater antibody titers. Our findings reject the hypothesis that androgens suppress immune function; rather, androgens may be immunoenhancing to acquired humoral responses and neutral to innate humoral immunity in crocodilians. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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42. Sensory neuronal control of skin barrier immunity.
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Feng, Xinyi, Zhan, Haoting, and Sokol, Caroline L.
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- *
SENSORY neurons , *CELL populations , *CELL physiology , *IMMUNITY , *DENDRITIC cells , *ITCHING - Abstract
Skin-innervating sensory neurons recognize a diverse array of exogenous and endogenous stimuli, including pathogens, allergens, tissue-derived alarmins, and immune-derived cytokines. Neuropeptides derived from sensory neurons signal to immune cells in the skin to promote or dampen innate immune responses to external insults. Sensory neurons influence the mode and magnitude of antigen-specific adaptive cutaneous immune responses by altering dendritic cell activation, migration, and priming of naïve T cells. Dendritic cell populations in mouse skin and skin-draining lymph nodes express mRNAs of numerous neuropeptide receptor genes, presenting ample opportunities for future investigation into neuronal control of cutaneous immunity. Skin-innervating sensory neurons detect noxious stimuli and release neuropeptides to control and shape mammalian innate and adaptive immune responses to external insults. Peripheral sensory neurons recognize diverse noxious stimuli, including microbial products and allergens traditionally thought to be targets of the mammalian immune system. Activation of sensory neurons by these stimuli leads to pain and itch responses as well as the release of neuropeptides that interact with their cognate receptors expressed on immune cells, such as dendritic cells (DCs). Neuronal control of immune cell function through neuropeptide release not only affects local inflammatory responses but can impact adaptive immune responses through downstream effects on T cell priming. Numerous neuropeptide receptors are expressed by DCs but only a few have been characterized, presenting opportunities for further investigation of the pathways by which cutaneous neuroimmune interactions modulate host immunity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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43. Innate and adaptive immune responses in subjects with CPA secondary to post‐pulmonary tuberculosis lung abnormalities.
- Author
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Chirumamilla, Naresh Kumar, Arora, Kanika, Kaur, Mandeep, Agarwal, Ritesh, Muthu, Valliappan, Rawat, Amit, Dhooria, Sahajal, Prasad, Kuruswamy Thurai, Aggarwal, Ashutosh Nath, Rudramurthy, Shivaprakash M., Chakrabarti, Arunaloke, Choudhary, Hansraj, Pal, Arnab, and Sehgal, Inderpaul Singh
- Subjects
- *
IMMUNE response , *LYMPHOCYTE subsets , *PULMONARY aspergillosis , *T cells , *B cells , *TUBERCULOSIS , *LUNGS , *IMMUNOGLOBULIN M - Abstract
Background: Post‐tuberculosis lung abnormality (PTLA) is the most common risk factor for chronic pulmonary aspergillosis (CPA), and 14%–25% of the subjects with PTLA develop CPA. The pathogenesis and the host immune response in subjects with PTLA who develop CPA need to be better understood. Methods: We prospectively compared the innate and adaptive immune responses mounted by patients of PTLA with or without CPA (controls). We studied the neutrophil oxidative burst (by dihydrorhodamine 123 test), classic (serum C3 and C4 levels) and alternative (mannose‐binding lectin [MBL] protein levels) complement pathway, serum immunoglobulins (IgG, IgM and IgA), B and T lymphocytes and their subsets in subjects with PTLA with or without CPA. Results: We included 111 subjects (58 CPA and 53 controls) in the current study. The mean ± SD age of the study population was 42.6 ± 15.7 years. The cases and controls were matched for age, gender distribution and body weight. Subjects with CPA had impaired neutrophil oxidative burst, lower memory T lymphocytes and impaired Th‐1 immune response (lower Th‐1 lymphocytes) than controls. We found no significant difference between the two groups in the serum complement levels, MBL levels, B‐cell subsets and other T lymphocyte subsets. Conclusion: Subjects with CPA secondary to PTLA have impaired neutrophil oxidative burst and a lower Th‐1 response than controls. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Genetic Screening Revealed the Negative Regulation of miR-310~313 Cluster Members on Imd Pathway during Gram-Negative Bacterial Infection in Drosophila.
- Author
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Li, Yao, Sun, Yixuan, Li, Ruimin, Zhou, Hongjian, Li, Shengjie, and Jin, Ping
- Subjects
- *
GENETIC testing , *GRAM-negative bacterial diseases , *GENE expression , *DROSOPHILA , *ESCHERICHIA coli - Abstract
Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in Drosophila melanogaster. However, the synergistical regulation of miRNAs located within a cluster on the Imd-immune pathway remains obscured. In our study, a genetic screening with 52 transgenic UAS-miRNAs was performed to identify ten miRNAs or miRNA clusters, including the miR310~313 cluster, which may function on Imd-dependent immune responses. The miRNA RT-qPCR analysis showed that the expression of miR-310~313 cluster members exhibited an increase at 6–12 h post E. coli infection. Furthermore, the overexpression of the miR-310~313 cluster impaired the Drosophila survival. And the overexpression of miR-310/311/312 reduced Dpt expression, an indication of Imd pathway induced by Gram-negative bacteria. Conversely, the knockdown of miR-310/311/312 led to increases in Dpt expression. The Luciferase reporter expression assays and RT-qPCR analysis confirmed that miR-310~313 cluster members directly co-targeted and inhibited Imd transcription. These findings reveal that the members of the miR-310~313 cluster synergistically inhibit Imd-dependent immune responses by co-targeting the Imd gene in Drosophila. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Exploring new perspectives in immunology.
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Medzhitov, Ruslan and Iwasaki, Akiko
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IMMUNOLOGIC memory , *IMMUNOLOGY , *ANTIGEN receptors , *NATURAL immunity , *IMMUNE response - Abstract
Several conceptual pillars form the foundation of modern immunology, including the clonal selection theory, antigen receptor diversity, immune memory, and innate control of adaptive immunity. However, some immunological phenomena cannot be explained by the current framework. Thus, we still do not know how to design vaccines that would provide long-lasting protective immunity against certain pathogens, why autoimmune responses target some antigens and not others, or why the immune response to infection sometimes does more harm than good. Understanding some of these mysteries may require that we question existing assumptions to develop and test alternative explanations. Immunology is increasingly at a point when, once again, exploring new perspectives becomes a necessity. Despite deep knowledge of how the immune system works, many questions remain difficult to answer within the current core framework of innate and adaptive immunity. This perspective highlights open questions where a change in the conceptual approach could be transformative for addressing persistent challenges to human health. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Endogenous IFN‐γ facilitates Pneumocystis infection and downregulates carbohydrate receptors in CD4+ T cell‐depleted mice.
- Author
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Wang, Yi, Nagase, Hisashi, Tagawa, Yoh‐ichi, Taki, Shinsuke, and Takamoto, Masaya
- Abstract
IFN‐γ plays a critical role in host defense against intracellular pathogens. IFN‐γ is produced in the bronchoalveolar lavage fluid of mice infected with Pneumocystis, but the role of IFN‐γ in host defense against Pneumocystis remains controversial. It has been previously reported that although exogenous IFN‐γ has beneficial effects on eradication of Pneumocystis, endogenous IFN‐γ has a negative impact on innate immunity in immunocompromised hosts. Surprisingly, CD4+ T cell‐depleted IFN‐γ deficient (GKO) mice exhibit resistance to Pneumocystis. Alveolar macrophages (AM) from GKO mice exhibit higher expression of macrophage mannose receptor (MMR) and Dectin‐1. Concomitantly, they exhibited greater ability to phagocytize Pneumocystis, and this activity was suppressed by inhibitors of these receptors. Incubation with IFN‐γ resulted in a reduction in both the expression of these receptors on AM and their Pneumocystis‐phagocytic activity. These results indicate that endogenous IFN‐γ facilitates Pneumocystis to escape from host innate immunity by attenuating the phagocytic activity of AM via downregulation of MMR and Dectin‐1. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. The Effects of Artificial Diets on the Expression of Molecular Marker Genes Related to Honey Bee Health.
- Author
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Frunze, Olga, Kim, Hyunjee, Lee, Jeong-Hyeon, and Kwon, Hyung-Wook
- Subjects
- *
HONEYBEES , *PROPOLIS , *DIET , *BEE colonies , *BEEKEEPING , *GENES , *MACHINE learning - Abstract
Honey bees are commonly used to study metabolic processes, yet the molecular mechanisms underlying nutrient transformation, particularly proteins and their effects on development, health, and diseases, still evoke varying opinions among researchers. To address this gap, we investigated the digestibility and transformation of water-soluble proteins from four artificial diets in long-lived honey bee populations (Apis mellifera ligustica), alongside their impact on metabolism and DWV relative expression ratio, using transcriptomic and protein quantification methods. Diet 2, characterized by its high protein content and digestibility, was selected for further analysis from the other studied diets. Subsequently, machine learning was employed to identify six diet-related molecular markers: SOD1, Trxr1, defensin2, JHAMT, TOR1, and vg. The expression levels of these markers were found to resemble those of honey bees who were fed with Diet 2 and bee bread, renowned as the best natural food. Notably, honey bees exhibiting chalkbrood symptoms (Control-N) responded differently to the diet, underscoring the unique nutritional effects on health-deficient bees. Additionally, we proposed a molecular model to elucidate the transition of long-lived honey bees from diapause to development, induced by nutrition. These findings carry implications for nutritional research and beekeeping, underscoring the vital role of honey bees in agriculture. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
48. Dietary Peppermint Extract Inhibits Chronic Heat Stress-Induced Activation of Innate Immunity and Inflammatory Response in the Spleen of Broiler Chickens.
- Author
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Ma, Dandan, Zhang, Minhong, and Feng, Jinghai
- Subjects
- *
NATURAL immunity , *BROILER chickens , *INFLAMMATION , *HEAT shock proteins , *PATTERN perception receptors , *HEAT shock factors , *PEPPERMINT - Abstract
Simple Summary: Heat stress is an important stressor in poultry husbandry with the rise in global temperature. Heat stress causes immune dysfunction and inflammatory responses in broiler chickens. Supplementation with plant extracts, which can be used to improve immune function and alleviate inflammatory response, can be an effective nutritional intervention. This study evaluated the effect of peppermint extract on the morphological changes and major pattern recognition receptors (PRRs) related to innate immunity and inflammatory response in the spleen of broiler chickens under chronic heat stress. Dietary peppermint extract inhibits chronic heat stress-induced activation of innate immunity and inflammatory response in the spleen of broiler chickens. Therefore, the supplementation with peppermint extract can be used to regulate innate immunity and inflammatory response in broiler chickens. The aim of this study was to investigate the effect of dietary peppermint extract (PE) on innate immunity and inflammatory responses in the spleen of broiler chickens under chronic heat stress. In order to further study the mechanism of the activation of innate immunity and inflammation induced by chronic heat stress and the regulatory effect of peppermint extract, we examined the spleen's histological change, the mRNA expression of major pattern recognition receptors (PRRs) (TLR2, TLR4, NOD1, MDA5 and DAI) and transcription factors (NF-κB, AP-1 and IRF3) and downstream inflammatory cytokines (IFN-α, IFN-β, IL-1β, IL-6 and TNF-α) of innate immune signaling pathways associated with heat stress in the spleen of broiler chickens. The results indicated that chronic heat stress damaged the spleen tissue. In addition, chronic heat stress induced the activation of innate immunity and inflammatory responses by increasing the mRNA expression of TLR2, TLR4 and DAI, mRNA expression of transcriptional factors (NF-κB, AP-1 and IRF3) and the concentration of downstream inflammatory cytokines in the spleen of broiler chickens. Dietary peppermint extract alleviated the damage of spleen tissue caused by chronic heat stress. In addition, peppermint extract reduced the mRNA expression of DAI, mRNA expression of transcriptional factors NF-κB, AP-1 and IRF3, and the concentration of inflammatory cytokines in the spleen of broiler chickens under chronic heat stress. In conclusion, dietary peppermint extract could have a beneficial effect on regulating inflammatory response and innate immunity via inhibiting the activation of NF-κB, AP-1 and IRF3 signaling pathways mediated by DAI in the spleen of broiler chickens induced by chronic heat stress. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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49. Molecular Characterization and Expression Analysis of the C-Type Lectin Domain Family 4 Member F in Litopenaeus vannamei against White Spot Syndrome Virus.
- Author
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Xue, Qian, Yang, Bingbing, Luo, Kun, Luan, Sheng, Kong, Jie, Li, Xupeng, and Meng, Xianhong
- Subjects
- *
WHITE spot syndrome virus , *WHITELEG shrimp , *GENE expression , *SHRIMP culture , *PATTERN perception receptors , *RNA interference - Abstract
Simple Summary: Outbreaks of white spot disease in Pacific white shrimp pose a significant threat to the major shrimp farming industry. Understanding the mechanisms of the shrimp against the causative virus is crucial. C-type lectins are important pattern recognition receptors that can be involved in the response against viral infections. This study identified the C-type lectin domain family 4 member F in shrimp as an important receptor gene that could promote replication of the causative virus and affect the survival rate of shrimp. This study will provide a theoretical basis for understanding the resistance mechanisms of shrimp against the virus. White spot disease (WSD) outbreaks pose a significant threat to the Pacific white shrimp (Litopenaeus vannamei) farming industry. The causative agent is the white spot syndrome virus (WSSV). There are no effective treatments for WSD so far. Therefore, understanding the resistance mechanisms of L. vannamei against the WSSV is crucial. C-type lectins (CTLs) are important pattern recognition receptors (PRRs) that promote agglutination, phagocytosis, encapsulation, bacteriostasis, and antiviral infections. This study cloned the C-type lectin domain family 4 member F (LvCLEC4F) from L. vannamei. LvCLEC4F contains a 492 bp open reading frame (ORF) encoding a protein of 163 amino acids, including a carbohydrate recognition domain (CRD). Following a challenge with the WSSV, the expression profile of LvCLEC4F was significantly altered. Using RNA interference (RNAi) technology, it was found that LvCLEC4F promotes WSSV replication and affects the expression levels of genes related to the regulation of apoptosis, signaling and cellular stress response, and immune defense. Meanwhile, the hemolymph agglutination phenomenon in vivo was weakened when LvCLEC4F was knocked down. These results indicated that LvCLEC4F may play an important role in the interaction between L. vannamei and WSSV. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. Immunotherapy with an antibody against CD1d modulates neuroinflammation in an α-synuclein transgenic model of Lewy body like disease.
- Author
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Iba, Michiyo, Kwon, Somin, Kim, Changyoun, Szabo, Marcell, Horan-Portelance, Liam, Lopez-Ocasio, Maria, Dagur, Pradeep, Overk, Cassia, Rissman, Robert A., and Masliah, Eliezer
- Subjects
- *
LEWY body dementia , *KILLER cells , *CYTOTOXIC T cells , *ANTIGEN presenting cells , *ALPHA-synuclein , *BLUNT trauma - Abstract
The neuroinflammatory process in synucleinopathies of the aging population such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB) involves microglial activation as well as infiltration of the CNS by T cells and natural killer T cells (NKTs). To evaluate the potential of targeting NKT cells to modulate neuroinflammation, we treated α-syn transgenic (tg) mice (e.g.: Thy1 promoter line 61) with an antibody against CD1d, which is a glycoprotein expressed in antigen presenting cells (APCs). CD1d-presented lipid antigens activate NKT cells through the interaction with T cell receptor in NKTs, resulting in the production of cytokines. Thus, we hypothesized that blocking the APC-NKT interaction with an anti-CD1d antibody might reduce neuroinflammation and neurodegeneration in models of DLB/PD. Treatment with the anti-CD1d antibody did not have effects on CD3 (T cells), slightly decreased CD4 and increased CD8 lymphocytes in the mice. Moreover, double labeling studies showed that compared to control (IgG) treated α-syn tg mice, treatment with anti-CD1d decreased numbers of CD3/interferon γ (IFN γ)-positive cells, consistent with NKTs. Further double labeling studies showed that CD1d-positive cells co-localized with the astrocytes marker GFAP and that anti-CD1d antibody reduced this effect. While in control α-syn tg mice CD3 positive cells were near astrocytes, this was modified by the treatment with the CD1d antibody. By qPCR, levels of IFN γ, CCL4, and interleukin-6 were increased in the IgG treated α-syn tg mice. Treatment with CD1d antibody blunted this cytokine response that was associated with reduced astrocytosis and microgliosis in the CNS of the α-syn tg mice treated with CD1d antibody. Flow cytometric analysis of immune cells in α-syn tg mice revealed that CD1d-tet + T cells were also increased in the spleen of α-syn tg mice, which treatment with the CD1d antibody reduced. Reduced neuroinflammation in the anti-CD1d-treated α-syn tg mice was associated with amelioration of neurodegenerative pathology. These results suggest that reducing infiltration of NKT cells with an antibody against CD1d might be a potential therapeutical approach for DLB/PD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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