Search

Acanthamoeba, are ubiquitous eukaryotic microorganisms, that play a pivotal role in recognizing and engulfing various microbes during predation, offering insights into microbial dynamics and immune responses. An intriguing observation lies in the apparent preference of Acanthamoeba for Gram-negative over Gram-positive bacteria, suggesting potential differences in the recognition and response mechanisms to bacterial prey. Here, we comprehensively review pattern recognition receptors (PRRs) and microbe associated molecular patterns (MAMPs) that influence Acanthamoeba interactions with bacteria. We analyze the molecular mechanisms underlying these interactions, and the key finding of this review is that Acanthamoeba exhibits an affinity for bacterial cell surface appendages that are decorated with carbohydrates. Notably, this parallels warm-blooded immune cells, underscoring a conserved evolutionary strategy in microbial recognition. This review aims to serve as a foundation for exploring PRRs and MAMPs. These insights enhance our understanding of ecological and evolutionary dynamics in microbial interactions and shed light on fundamental principles governing immune responses. Leveraging Acanthamoeba as a model organism, provides a bridge between ecological interactions and immunology, offering valuable perspectives for future research. [ABSTRACT FROM AUTHOR]

Insects are known to dominate adverse ecological conditions due to their diverse adaptations and resilient biological traits, with their immune systems playing a crucial role in this dominance. Traditionally, insects were thought to lack adaptive immune responses due to their inability to produce antibodies and transfer immunity across generations. However, recent research using insects as model organisms has challenged this notion, revealing that prior exposure to sublethal doses of pathogens or pathogen‐derived materials can protect against subsequent lethal exposures—a phenomenon known as ‘immune priming’. Evidence of bacterial, fungal and viral immune priming across different insect species highlights various types of priming, including trans‐stadial (across life stages) and trans‐generational (across generations) priming. Despite differing views on immune priming, its potential applications in agriculture are considerable, especially in biological control, the utilization of beneficial insects and sustainable pest management. This review explores the intricate dynamics of immune priming in insects, comparing it to vertebrate immunity and investigates its mechanisms, potential agricultural applications and future prospects. [ABSTRACT FROM AUTHOR]

Phytophthora cinnamomi Rands devastates forest species worldwide, causing significant ecological and economic impacts. The European chestnut (Castanea sativa) is susceptible to this hemibiotrophic oomycete, whereas the Asian chestnuts (Castanea crenata and Castanea mollissima) are resistant and have been successfully used as resistance donors in breeding programs. The molecular mechanisms underlying the different disease outcomes among chestnut species are a key foundation for developing science-based control strategies. However, these are still poorly understood. Dual RNA sequencing was performed in C. sativa and C. crenata roots inoculated with P. cinnamomi. The studied time points represent the pathogen's hemibiotrophic lifestyle previously described at the cellular level. Phytophthora cinnamomi expressed several genes related to pathogenicity in both chestnut species, such as cell wall-degrading enzymes, host nutrient uptake transporters, and effectors. However, the expression of effectors related to the modulation of host programmed cell death (elicitins and NLPs) and sporulation-related genes was higher in the susceptible chestnut. After pathogen inoculation, 1,556 and 488 genes were differentially expressed by C. crenata and C. sativa, respectively. The most significant transcriptional changes occur at 2 h after inoculation (hai) in C. sativa and 48 hai in C. crenata. Nevertheless, C. crenata induced more defense-related genes, indicating that the resistant response to P. cinnamomi is controlled by multiple loci, including several pattern recognition receptors, genes involved in the phenylpropanoid, salicylic acid and ethylene/jasmonic acid pathways, and antifungal genes. Importantly, these results validate previously observed cellular responses for C. crenata. Collectively, this study provides a comprehensive time-resolved description of the chestnut-P. cinnamomi dynamic, revealing new insights into susceptible and resistant host responses and important pathogen strategies involved in disease development. [ABSTRACT FROM AUTHOR]

We previously showed that several polymorphisms in genes encoding pattern recognition receptors that cause amino acid substitutions alter pathogen recognition ability and disease susceptibility in pigs. In this study, we expanded our analysis to a wide range of immune-related genes and investigated polymorphism distribution and its influence on pneumonia in multiple commercial pig populations. Among the polymorphisms in 42 genes causing 634 amino acid substitutions extracted from the swine genome database, 80 in 24 genes were found to have a minor allele frequency of at least 10% in Japanese breeding stock pigs via targeted resequencing. Of these, 62 single nucleotide polymorphisms (SNPs) in 23 genes were successfully genotyped in 862 pigs belonging to four populations with data on pneumonia severity. Association analysis using a generalized linear mixed model revealed that 12 SNPs in nine genes were associated with pneumonia severity. In particular, SNPs in the cellular receptor for immunoglobulin G FCGR2B and the intracellular nucleic acid sensors IFI16 and LRRFIP1 were found to be associated with mycoplasmal pneumonia of swine or porcine pleuropneumonia in multiple populations and may therefore have wide applications in the improvement of disease resistance in pigs. Functional analyses at the cellular and animal levels are required to clarify the mechanisms underlying the effects of these SNPs on disease susceptibility. [ABSTRACT FROM AUTHOR]

The cyclic GMP–AMP synthase (cGAS), a prominent intracellular DNA sensor in mammalian cells, controls the innate immune response and the stimulator of interferon genes (STING)‐mediated synthesis of pro‐inflammatory cytokines, such as type‐I interferon (IFN‐I). For decades, IFN‐I has been hypothesized to be essential in the development of systemic lupus erythematosus (SLE), a chronic multisystem autoimmunity characterized by immune complex (IC) deposition in small vessels. Recent findings revealed that the activation of the cGAS–STING pathway by self‐DNA would propagate the autoimmune responses via upregulating IFN‐I production in SLE. In this review, we aimed to provide a comprehensive outlook of the role of the cGAS–STING pathway in SLE pathobiology, as well as, a better understanding of current therapeutic opportunities targeting this axis. [ABSTRACT FROM AUTHOR]

Cutaneous hypersensitivity reactions (CHRs) are complex inflammatory skin disorders that affect humans and dogs. This study examined the inflammatory and immune responses leading to skin damage, inflammation, and irritation by investigating gene expression through quantitative PCR (qPCR) and protein localization through the immunohistochemistry (IHC) of specific receptors and molecules involved in CHRs. Formalin-fixed paraffin-embedded (FFPE) samples from canine CHR skin (n = 20) and healthy dog skin (n = 3) were analyzed for expression levels of eight genes, including members of the pattern recognition receptor (PRR) family, CD209 and CLEC4G, the Regakine-1-like chemokine, and acute phase proteins (APPs), LBP-like and Hp-like genes. Additionally, we examined the local involvement of IL-6, Janus Kinase 1 (JAK1), and the signal transducer activator of transcription 3 (STAT3) in the CHR cases. The study demonstrated statistically significant increases in the expression levels of CD209, Hp-like (p < 0.01), LBP-like, Regakine-1-like, and CLEC4G (p < 0.05) genes in CHRs compared to healthy controls. Conversely, IL-6, JAK1, and STAT3 showed no significant difference between the two groups (p > 0.05). Protein analysis revealed JAK1 and STAT3 expression in CHR hyperplastic epithelial cells, dermal fibroblasts, and endothelial cells of small capillaries, indicating a possible involvement in the JAK/STAT pathway in local inflammatory response regulation. Our findings suggest that the skin plays a role in the development of CHRs.

Background: Irritable bowel syndrome is a functional gastrointestinal disease of unknown etiology. Researchers have recently drawn attention to the possible role of viruses in the development of IBS and provided evidence in this regard. In this study, it was decided to investigate the possible role of rotavirus infection in the onset of IBS.Methods: Stool and serum samples were collected from 40 patients with IBS and 40 healthy individuals. To evaluate the previous exposure to rotavirus we checked the presence and concentration of anti-rotavirus IgG by ELISA. ELISA test was performed on the serum samples. Real-time PCR test was also used to measure the viral load in the stool. Finally, the data were analyzed by SPSS-22 software.Results: No significant relationship was found between anti-rotavirus IgG presence and Level in the serum of case and healthy individuals (p-value > 0.05) . Moreover, there was no significant difference between the viral genome load in the stool samples of the two groups (p-value > 0.05).Conclusion: According to the results, it seems unlikely that a link exists between rotavirus infection and the onset of irritable bowel syndrome, but the possible role of other gastrointestinal viruses, including coronavirus, remains.

Jingjing Wang,1 Yirui Dong,1 Xuewei Zheng,1 Haodi Ma,1 Mengjiao Huang,1 Dongliao Fu,1 Jiangbo Liu,2 Qinan Yin1,3 1School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, People’s Republic of China; 2Department of General Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Henan Engineering Research Center of Digital Pathology and Artificial Intelligence Diagnosis, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, People’s Republic of ChinaCorrespondence: Qinan Yin, School of Medical Technology and Engineering, Henan University of Science and Technology, No. 263 Kaiyuan Avenue, Luoyang, People’s Republic of China, 471003, Email qinanyin@haust.edu.cn Jiangbo Liu, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Guanlin Avenue, Luoyang, 471031, People’s Republic of China, Email jiangboliuxing@163.comAbstract: Innate immunity is the first line of defense in the human body, and it plays an important role in defending against viral infection. Viruses are identified by different pattern-recognition receptors (PRRs) that activate the mitochondrial antiviral signaling protein (MAVS) or transmembrane protein 173 (STING), which trigger multiple signaling cascades that cause nuclear factor-κB (NF-κB) and interferon regulatory factor 3 (IRF3) to produce inflammatory factors and interferons (IFNs). PRRs play a pivotal role as the first step in pathogen induction of interferon production. Interferon elicits antiviral activity by inducing the transcription of hundreds of IFN-stimulated genes (ISGs) via the janus kinase (JAK) – signal transducer and activator of transcription (STAT) pathway. An increasing number of studies have shown that environmental, pathogen and host factors regulate the IFN signaling pathway. Here, we summarize the mechanisms of host factor modulation in IFN production via pattern recognition receptors. These regulatory mechanisms maintain interferon levels in a normal state and clear viruses without inducing autoimmune disease.Keywords: pattern recognition receptors, interferon-signaling pathway, host factors

Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced to 20% in aged mice (85–112 weeks) versus 50% in young mice (12–15 weeks) at 10 days post infection (dpi). Bulk RNA-sequencing of endothelial cells from mock and infected mice at 2dpi of both age groups (aged: 72–85 weeks; young: 15 weeks) showed substantially lower significant differentially regulated genes in infected aged mice than in young mice (712 versus 2294 genes). Viral recognition and anti-viral pathways such as RIG-I-like receptor signaling, NOD-like receptor signaling and interferon signaling were regulated in response to SARS-CoV-2. Young mice showed several fold higher interferon responses (Ifitm3, Ifit1, Isg15, Stat1) and interferon-induced chemokines (Cxcl10 and Cxcl11) than aged mice. Endothelial cells from infected young mice displayed elevated expression of chemokines (Cxcl9, Ccl2) and leukocyte adhesion markers (Icam1) underscoring that inflammation of lung endothelium during infection could facilitate leukocyte adhesion and thromboinflammation. TREM1 and acute phase response signaling were particularly prominent in endothelial cells from infected young mice. Immunohistochemistry was unable to detect viral protein in pulmonary endothelium. In conclusion, our data demonstrate that the early host response of the endothelium to SARS-CoV-2 infection declines with aging, which could be a potential contributor to disease severity. [ABSTRACT FROM AUTHOR]

Innate immune defense mechanisms against infection and cancer encompass the modulation of pattern recognition receptor (PRR)‐mediated inflammation, including upregulation of various transcription factors and the activation of pro‐inflammatory pathways important for immune surveillance. Dysfunction of PRRs‐mediated signaling has been implicated in cancer and autoimmune diseases, while the overactivation of PRRs‐driven responses during infection can lead to devastating consequences such as acute lung injury or sepsis. We used crystal structure‐based design to develop immunomodulatory lipopolysaccharide (LPS) mimetics targeting one of the ubiquitous PRRs, Toll‐like Receptor 4 (TLR4). Taking advantage of an exo‐anomeric conformation and specific molecular shape of synthetic nonreducing β,β‐diglucosamine, which was investigated by NMR, we developed two sets of lipid A mimicking glycolipids capable of either potently activating innate immune responses or inhibiting pro‐inflammatory signaling. Stereoselective 1,1′‐glycosylation towards fully orthogonally protected nonreducing GlcNβ(1↔1′)βGlcN followed by stepwise assembly of differently functionalised phosphorylated glycolipids provided biologically active molecules that were evaluated for their ability to trigger or to inhibit cellular innate immune responses. Two LPS mimetics, identified as potent TLR4‐specific inducers of the intracellular signaling pathways, serve as vaccine adjuvant‐ and immunotherapy candidates, while anionic glycolipids with TLR4‐inhibitory potential hold therapeutic promise for the management of acute or chronic inflammation. [ABSTRACT FROM AUTHOR]

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis. [ABSTRACT FROM AUTHOR]

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co‐operators of oncogenic KRAS in the lung remains ill‐defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent‐in‐melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS‐addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine‐derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome‐associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK‐induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D‐driven LAC in both hematopoietic (immune) and non‐hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2‐deficient mice is associated with unaltered protein levels of mature Caspase‐1 and IL‐1β inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D‐driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase‐1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor‐promoting role, independent of inflammasomes, in mutant KRAS‐addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer. [ABSTRACT FROM AUTHOR]

Microglia directly sense neurotransmitters, including norepinephrine and γ-aminobutyric acid (GABA), which act as 'brain-associated molecular patterns' to shape neuronal connectivity. Cytokines can instruct distinct microglial functional states. Microglia contact different sites on neuronal bodies, from the dendrite to the soma to the axon, using activity-dependent mechanisms, including purinergic sensing via P2Y12. Microglia can transiently alter synaptic function by interposing between pre- and post-synaptic membranes; they can also alter synapse numbers by remodeling connections. Microglia (tissue-resident macrophages of the brain) dynamically regulate healthy brain function and connectivity by directly sensing molecular patterns associated with neuronal activity, which include neurotransmitters, purines, and portions of remodeling neural circuits. Microglia are brain-resident macrophages that play key roles in brain development and experience dependent plasticity. In this review we discuss recent findings regarding the molecular mechanisms through which mammalian microglia sense the unique molecular patterns of the homeostatic brain. We propose that microglial function is acutely controlled in response to 'brain-associated molecular patterns' (BAMPs) that function as indicators of neuronal activity and neural circuit remodeling. A further layer of regulation comes from instructive cytokine cues that define unique microglial functional states. A systematic investigation of the receptors and signaling pathways that mediate these two regulatory axes may begin to define a functional code for microglia–neuron interactions. [ABSTRACT FROM AUTHOR]

C-type lectins in organisms play an important role in the process of innate immunity. In this study, a C-type lectin belonging to the DC-SIGN class of Micropterus salmoides was identified. MsDC-SIGN is classified as a type II transmembrane protein. The extracellular segment of MsDC-SIGN possesses a coiled-coil region and a carbohydrate recognition domain (CRD). The key amino acid motifs of the extracellular CRD of MsDC-SIGN in Ca2+-binding site 2 were EPN (Glu-Pro-Asn) and WYD (Trp-Tyr-Asp). MsDC-SIGN-CRD can bind to four pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), glucan, peptidoglycan (PGN), and mannan. Moreover, it can also bind to Gram-positive, Gram-negative bacteria, and fungi. Its CRD can agglutinate microbes and displays D-mannose and D-galactose binding specificity. MsDC-SIGN was distributed in seven tissues of the largemouth bass, among which the highest expression was observed in the liver, followed by the spleen and intestine. Additionally, MsDC-SIGN was present on the membrane of M. salmoides leukocytes, thereby augmenting the phagocytic activity against bacteria. In a subsequent investigation, the expression patterns of the MsDC-SIGN gene and key genes associated with the TLR signaling pathway (TLR4, NF-κB, and IL10) exhibited an up-regulated expression response to the stimulation of Aeromonas hydrophila. Furthermore, through RNA interference of MsDC-SIGN, the expression level of the DC-SIGN signaling pathway-related gene (RAF1) and key genes associated with the TLR signaling pathway (TLR4, NF-κB, and IL10) was decreased. Therefore, MsDC-SIGN plays a pivotal role in the immune defense against A. hydrophila by modulating the TLR signaling pathway. [ABSTRACT FROM AUTHOR]

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment that utilizes viruses to preferentially infect and eliminate cancer cells while stimulating the immune response. In this review, we synthesize the current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy, focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated-signal sensing by neighboring cells, and the subsequent downstream activation of immune pathways. These sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how the molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting-cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies. [ABSTRACT FROM AUTHOR]

Bacillus pumilus TUAT1 acts as plant growth–promoting rhizobacteria for various plants like rice and Arabidopsis. Under stress conditions, B. pumilus TUAT1 forms spores with a thick peptidoglycan (PGN) cell wall. Previous research showed that spores were significantly more effective than vegetative cells in enhancing plant growth. In Arabidopsis , lysin motif proteins, LYM1, LYM3 and CERK1, are required for recognizing bacterial PGNs to mediate immunity. Here, we examined the involvement of PGN receptor proteins in the plant growth promotion (PGP) effects of B. pumilus TUAT1 using Arabidopsis mutants defective in PGN receptors. Root growth of wild-type (WT), cerk1-1, lym1-1 and lym1-2 mutant plants was significantly increased by TUAT1 inoculation, but this was not the case for lym3-1 and lym3-2 mutant plants. RNA-seq analysis revealed that the expression of a number of defense-related genes was upregulated in lym3 mutant plants. These results suggested that B. pumilus TUAT1 may act to reduce the defense response, which is dependent on a functional LYM3. The expression of the defense-responsive gene, WRKY29 , was significantly induced by the elicitor flg-22, in both WT and lym3 mutant plants, while this induction was significantly reduced by treatment with B. pumilus TUAT1 and PGNs in WT, but not in lym3 mutant plants. These findings suggest that the PGNs of B. pumilus TUAT1 may be recognized by the LYM3 receptor protein, suppressing the defense response, which results in plant growth promotion in a trade-off between defense and growth. [ABSTRACT FROM AUTHOR]

Neuropsychiatric disorders denote a broad range of illnesses involving neurology and psychiatry. These disorders include depressive disorders, anxiety, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorders, headaches, and epilepsy. In addition to their main neuropathology that lies in the central nervous system (CNS), lately, studies have highlighted the role of immunity and neuroinflammation in neuropsychiatric disorders. Toll‐like receptors (TLRs) are innate receptors that act as a bridge between the innate and adaptive immune systems via adaptor proteins (e.g., MYD88) and downstream elements; TLRs are classified into 13 families that are involved in normal function and illnesses of the CNS. TLRs expression affects the course of neuropsychiatric disorders, and is influenced during their pharmacotherapy; For example, the expression of multiple TLRs is normalized during the major depressive disorder pharmacotherapy. Here, the role of TLRs in neuroimmunology, treatment, and management of neuropsychiatric disorders is discussed. We recommend longitudinal studies to comparatively assess the cell‐type‐specific expression of TLRs during treatment, illness progression, and remission. Also, further research should explore molecular insights into TLRs regulation and related pathways. [ABSTRACT FROM AUTHOR]

Recent research highlights that inflammatory signaling pathways such as pattern recognition receptor (PRR) signaling and inflammatory cytokine signaling play an important role in both on‐demand hematopoiesis as well as steady‐state hematopoiesis. Knockout studies have demonstrated the necessity of several distinct pathways in these processes, but often lack information about the contribution of specific cell types to the phenotypes in question. Transplantation studies have increased the resolution to the level of specific cell types by testing the necessity of inflammatory pathways specifically in donor hematopoietic stem and progenitor cells (HSPCs) or in recipient niche cells. Here, we argue that for an integrated understanding of how these processes occur in vivo and to inform the development of therapies that modulate hematopoietic responses, we need studies that knockout inflammatory signaling receptors in a cell‐specific manner and compare the phenotypes caused by knockout in individual niche cells versus HSPCs. [ABSTRACT FROM AUTHOR]

IntroductionAdjuvants added to subunit vaccines augment antigen-specific immune responses. One mechanism of adjuvant action is activation of pattern recognition receptors (PRRs) on innate immune cells. Bordetella colonization factor A (BcfA); an outer membrane protein with adjuvant function, activates TH1/TH17-polarized immune responses to protein antigens from Bordetella pertussis and SARS CoV-2. Unlike other adjuvants, BcfA does not elicit a TH2 response.MethodsTo understand the mechanism of BcfA-driven TH1/TH17 vs. TH2 activation, we screened PRRs to identify pathways activated by BcfA. We then tested the role of this receptor in the BcfA-mediated activation of bone marrow-derived dendritic cells (BMDCs) using mice with germline deletion of TLR4 to quantify upregulation of costimulatory molecule expression and cytokine production in vitro and in vivo. Activity was also tested on human PBMCs.ResultsPRR screening showed that BcfA activates antigen presenting cells through murine TLR4. BcfA-treated WT BMDCs upregulated expression of the costimulatory molecules CD40, CD80, and CD86 and produced IL-6, IL-12/23 p40, and TNF-α while TLR4 KO BMDCs were not activated. Furthermore, human PBMCs stimulated with BcfA produced IL-6. BcfA-stimulated murine BMDCs also exhibited increased uptake of the antigen DQ-OVA, supporting a role for BcfA in improving antigen presentation to T cells. BcfA further activated APCs in murine lungs. Using an in vitro TH cell polarization system, we found that BcfA-stimulated BMDC supernatant supported TFH and TH1 while suppressing TH2 gene programming.ConclusionsOverall, these data provide mechanistic understanding of how this novel adjuvant activates immune responses.

Acanthamoeba, are ubiquitous eukaryotic microorganisms, that play a pivotal role in recognizing and engulfing various microbes during predation, offering insights into microbial dynamics and immune responses. An intriguing observation lies in the apparent preference of Acanthamoeba for Gram-negative over Gram-positive bacteria, suggesting potential differences in the recognition and response mechanisms to bacterial prey. Here, we comprehensively review pattern recognition receptors (PRRs) and microbe associated molecular patterns (MAMPs) that influence Acanthamoeba interactions with bacteria. We analyze the molecular mechanisms underlying these interactions, and the key finding of this review is that Acanthamoeba exhibits an affinity for bacterial cell surface appendages that are decorated with carbohydrates. Notably, this parallels warm-blooded immune cells, underscoring a conserved evolutionary strategy in microbial recognition. This review aims to serve as a foundation for exploring PRRs and MAMPs. These insights enhance our understanding of ecological and evolutionary dynamics in microbial interactions and shed light on fundamental principles governing immune responses. Leveraging Acanthamoeba as a model organism, provides a bridge between ecological interactions and immunology, offering valuable perspectives for future research.

Phytophthora cinnamomi Rands devastates forest species worldwide, causing significant ecological and economic impacts. The European chestnut (Castanea sativa) is susceptible to this hemibiotrophic oomycete, whereas the Asian chestnuts (Castanea crenata and Castanea mollissima) are resistant and have been successfully used as resistance donors in breeding programs. The molecular mechanisms underlying the different disease outcomes among chestnut species are a key foundation for developing science-based control strategies. However, these are still poorly understood. Dual RNA sequencing was performed in C. sativa and C. crenata roots inoculated with P. cinnamomi. The studied time points represent the pathogen’s hemibiotrophic lifestyle previously described at the cellular level. Phytophthora cinnamomi expressed several genes related to pathogenicity in both chestnut species, such as cell wall–degrading enzymes, host nutrient uptake transporters, and effectors. However, the expression of effectors related to the modulation of host programmed cell death (elicitins and NLPs) and sporulation-related genes was higher in the susceptible chestnut. After pathogen inoculation, 1,556 and 488 genes were differentially expressed by C. crenata and C. sativa, respectively. The most significant transcriptional changes occur at 2 h after inoculation (hai) in C. sativa and 48 hai in C. crenata. Nevertheless, C. crenata induced more defense-related genes, indicating that the resistant response to P. cinnamomi is controlled by multiple loci, including several pattern recognition receptors, genes involved in the phenylpropanoid, salicylic acid and ethylene/jasmonic acid pathways, and antifungal genes. Importantly, these results validate previously observed cellular responses for C. crenata. Collectively, this study provides a comprehensive time-resolved description of the chestnut–P. cinnamomi dynamic, revealing new insights into susceptible and resistant host responses and important pathogen strategies involved in disease development.

This document is an editorial from the journal Frontiers in Immunology titled "Reviews in insect immune responses: 2022." The editorial introduces a research topic that explores the complexities of how insects defend themselves against pathogens and the implications of these defense mechanisms for both basic and applied sciences. The articles within this research topic cover a wide range of topics in insect immunology, including the role of miRNAs in bacterial infections, the function of pattern recognition receptors in immune responses, the immune signaling pathways in the insect gut, and the interaction between insects and entomopathogenic fungi. The editorial aims to provide a comprehensive overview of the field and inspire further research in insect immunology. [Extracted from the article]

ABSTRACTVaccines are an effective way to prevent the emergence and spread of antibiotic resistance by preventing diseases and establishing herd immunity. However, the reduced effectiveness of vaccines in the elderly due to immunosenescence is one of the significant contributors to the increasing antibiotic resistance. To counteract this decline and enhance vaccine effectiveness in the elderly, adjuvants play a pivotal role. Adjuvants are designed to augment the effectiveness of vaccines by activating the innate immune system, particularly through pattern recognition receptors on antigen-presenting cells. To improve vaccine effectiveness in the elderly using adjuvants, it is imperative to select the appropriate adjuvants based on an understanding of immunosenescence and the mechanisms of adjuvant functions. This review demonstrates the phenomenon of immunosenescence and explores various types of adjuvants, including their mechanisms and their potential in improving vaccine effectiveness for the elderly, thereby contributing to developing more effective vaccines for this vulnerable demographic.

Koi herpesvirus (KHV, CyHV-3) causes severe economic losses in carp farms. Its eradication is challenging due to the establishment of latency in blood leukocytes and other tissues. To understand the molecular mechanisms leading to KHV infection in leukocytes, common carp were bath-exposed to KHV at 17 °C. After confirming the presence of viral transcripts in blood leukocytes at ten days post infection, RNA-Seq was performed on peripheral blood leukocytes on the Illumina NovaSeq. KHV infection triggered a robust immune response mediated by pattern recognition receptors, mainly toll-like receptors (tlr2, tlr5, tlr7, and tlr13), urokinase plasminogen activator surface receptor-like, galectin proteins, and lipid mediators such as leukotriene B4 receptor 1. Enriched pathways showed increased mitochondria oxidative phosphorylation and the activation of signalling pathways such as mitogen-activated protein kinases (MAPKs) and vascular endothelial growth factor (VEGF). KHV-infected leukocytes showed low production of reactive oxygen species (ROS) and glutathione metabolism, high iron export and phagocytosis activity, and low autophagy. Macrophage polarization was deduced from the up-regulation of genes such as arginase non-hepatic 1-like, macrophage mannose receptor-1, crem, il-10, and il-13 receptors, while markers for cytotoxic T cells were observed to be down-regulated. Further work is required to characterise these leukocyte subsets and the molecular events leading to KHV latency in blood leukocytes. [ABSTRACT FROM AUTHOR]

Progress in the development of effective chemotherapy is producing a growing population of patients with acute and chronic painful chemotherapy-induced peripheral neuropathy (CIPN), a serious treatment-limiting side effect for which there is currently no US Food and Drug Administration-approved treatment. CIPNs induced by diverse classes of chemotherapy drugs have remarkably similar clinical presentations, leading to the suggestion they share underlying mechanisms. Sensory neurons share with immune cells the ability to detect damage associated molecular patterns (DAMPs), molecules produced by diverse cell types in response to cellular stress and injury, including by chemotherapy drugs. DAMPs, in turn, are ligands for pattern recognition receptors (PRRs), several of which are found on sensory neurons, as well as satellite cells, and cells of the immune system. In the present experiments, we evaluated the role of two PRRs, TLR4 and RAGE, present in dorsal root ganglion (DRG), in CIPN. Antisense (AS)-oligodeoxynucleotides (ODN) against TLR4 and RAGE mRNA were administered intrathecally before ('prevention protocol') or 3 days after ('reversal protocol') the last administration of each of three chemotherapy drugs that treat cancer by different mechanisms (oxaliplatin, paclitaxel and bortezomib). TLR4 and RAGE AS-ODN prevented the development of CIPN induced by all three chemotherapy drugs. In the reversal protocol, however, while TLR4 AS-ODN completely reversed oxaliplatin- and paclitaxel-induced CIPN, in rats with bortezomib-induced CIPN it only produced a temporary attenuation. RAGE AS-ODN, in contrast, reversed CIPN induced by all three chemotherapy drugs. When a TLR4 antagonist was administered intradermally to the peripheral nociceptor terminal, it did not affect CIPN induced by any of the chemotherapy drugs. However, when administered intrathecally, to the central terminal, it attenuated hyperalgesia induced by all three chemotherapy drugs, compatible with a role of TLR4 in neurotransmission at the central terminal but not sensory transduction at the peripheral terminal. Finally, since it has been established that cultured DRG neurons can be used to study direct effects of chemotherapy on nociceptors, we also evaluated the role of TLR4 in CIPN at the cellular level, using patch-clamp electrophysiology in DRG neurons cultured from control and chemotherapy-treated rats. We found that increased excitability of small-diameter DRG neurons induced by in vivo and in vitro exposure to oxaliplatin is TLR4-dependent. Our findings suggest that in addition to the established contribution of PRR-dependent neuroimmune mechanisms, PRRs in DRG cells also have an important role in CIPN. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) capture pathogens and process antigens, playing a crucial role in activating naïve T cells, bridging the gap between innate and acquired immunity. However, little is known about DC activation when facing Leishmania parasites. Thus, this study investigates in vitro activity of canine peripheral blood-derived DCs (moDCs) exposed to L. infantum and L. amazonensis parasites and their extracellular vesicles (EVs). L. infantum increased toll-like receptor 4 gene expression in synergy with nuclear factor κB activation and the generation of pro-inflammatory cytokines. This parasite also induced the expression of class II molecules of major histocompatibility complex (MHC) and upregulated co-stimulatory molecule CD86, which, together with the release of chemokine CXCL16, can attract and help in T lymphocyte activation. In contrast, L. amazonensis induced moDCs to generate a mix of pro- and anti-inflammatory cytokines, indicating that this parasite can establish a different immune relationship with DCs. EVs promoted moDCs to express class I MHC associated with the upregulation of co-stimulatory molecules and the release of CXCL16, suggesting that EVs can modulate moDCs to attract cytotoxic CD8+ T cells. Thus, these parasites and their EVs can shape DC activation. A detailed understanding of DC activation may open new avenues for the development of advanced leishmaniasis control strategies. [ABSTRACT FROM AUTHOR]

Summary: Type I interferon (IFN) is a class of proinflammatory cytokines with a dual role on malignant transformation, tumor progression, and response to therapy. On the one hand, robust, acute, and resolving type I IFN responses have been shown to mediate prominent anticancer effects, reflecting not only their direct cytostatic/cytotoxic activity on (at least some) malignant cells, but also their pronounced immunostimulatory functions. In line with this notion, type I IFN signaling has been implicated in the antineoplastic effects of various immunogenic therapeutics, including (but not limited to) immunogenic cell death (ICD)‐inducing agents and immune checkpoint inhibitors (ICIs). On the other hand, weak, indolent, and non‐resolving type I IFN responses have been demonstrated to support tumor progression and resistance to therapy, reflecting the ability of suboptimal type I IFN signaling to mediate cytoprotective activity, promote stemness, favor tolerance to chromosomal instability, and facilitate the establishment of an immunologically exhausted tumor microenvironment. Here, we review fundamental aspects of type I IFN signaling and their context‐dependent impact on malignant transformation, tumor progression, and response to therapy. [ABSTRACT FROM AUTHOR]

Breast cancer stands as a primary malignancy among women, ranking second in global cancer-related deaths. Despite treatment advancements, many patients progress to metastatic stages, posing a significant therapeutic challenge. Current therapies primarily target cancer cells, overlooking their intricate interactions with the tumor microenvironment (TME) that fuel progression and treatment resistance. Dysregulated innate immunity in breast cancer triggers chronic inflammation, fostering cancer development and therapy resistance. Innate immune pattern recognition receptors (PRRs) have emerged as crucial regulators of the immune response as well as of several immune-mediated or cancer cell-intrinsic mechanisms that either inhibit or promote tumor progression. In particular, several studies showed that the Toll-like receptor 2 (TLR2) and the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathways play a central role in breast cancer progression. In this review, we present a comprehensive overview of the role of TLR2 and STING in breast cancer, and we explore the potential to target these PRRs for drug development. This information will significantly impact the scientific discussion on the use of PRR agonists or inhibitors in cancer therapy, opening up new and promising avenues for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Problem: In women of reproductive age, endometriosis may contribute to dysmenorrhea, chronic pelvic pain, dyspareunia, infertility, adenomyosis, and endometrial ovarian cyst (EOC). Recent studies have shown that chronic inflammation occurs in the pelvis of endometriosis patients and that this inflammation is exacerbated by immunosuppression, leading to survival endometrial debris. However, the detailed immunological mechanisms underlying the aggravation of inflammation and immunosuppression in endometriosis patients remain unclear. Method of Study: We investigate the alarmins (high‐mobility group box‐1, IL‐33, IL‐1α, and S100B protein), proinflammatory cytokines (IL‐6 and IL‐1β), and immune cells (CD8+ T cells, CD4+ T cells, natural killer cells, natural killer T cells, dendritic cells, and macrophages) in peritoneal fluid of patients with EOC using enzyme‐linked immunosorbent assay, electrochemiluminescence, and flow cytometry. Then, we analyzed the correlation between these factors and the aggravating indicators of endometriosis, tumor size and revised American Society for Reproductive Medicine (r‐ASRM) score. Results: Unexpectedly, there was no correlation between each alarmin level and aggravating indicators. However, the expression of pattern recognition receptors, toll‐like receptor 4, and receptor of advanced glycation end‐products on macrophages was inversely correlated with aggravating indicators. Conclusions: The aggravation of endometriosis is associated with a decrease in alarmin receptors but not alarmin levels. Investigation of innate immune systems, such as alarmins and their receptors, may help elucidate new mechanisms of endometriosis. [ABSTRACT FROM AUTHOR]

Crustacean species are among the most valued seafood with socioeconomic and ecological implications in the global fisheries sector. Microbial infections to the farming stock due to continued expansion and aquaculture puts global crustacean production at risk. Understanding and reviewing the complex innate immune system of crustaceans would be pivotal in formulating informed decisions for the control and management of epidemic diseases, thus making the global crustacean aquaculture industry sustainable. Under the purview of innate immunity in crustaceans, pattern recognition receptors (PRRs) represent the sensors capable of discriminating non‐self pathogenic modules and invoking the activation of immune responses. The immunity to infections can be manifested at cellular (via phagocytosis, apoptosis, nodulation and encapsulation) and humoral (effected by prophenoloxidase cascade, lectins, antimicrobial proteins) levels leading to the elimination of pathogens or subversion of the pathogenic implications. In this review, we discuss the participatory role of 12 types of PRRs identified from crustacean species with an exhaustive focus on structural and functional specificities in binding to pathogens and possible execution of the immune activity. Moreover, we have elaborated on the PRRs‐associated or possible signalling cascades (Toll‐NFκB, IMD‐NFκB and JAK‐STAT) in crustacean species that could bridge our understanding of the resistance or susceptibility of the host to varied pathogenic infections thus providing clues to the regulatory mechanisms involved in pathogenesis of infectious diseases and mechanisms of immunity. [ABSTRACT FROM AUTHOR]

Advanced age is associated with an increased susceptibility to Coronavirus Disease (COVID)-19 and more severe outcomes, although the underlying mechanisms are understudied. The lung endothelium is located next to infected epithelial cells and bystander inflammation may contribute to thromboinflammation and COVID-19-associated coagulopathy. Here, we investigated age-associated SARS-CoV-2 pathogenesis and endothelial inflammatory responses using humanized K18-hACE2 mice. Survival was reduced to 20% in aged mice (85–112 weeks) versus 50% in young mice (12–15 weeks) at 10 days post infection (dpi). Bulk RNA-sequencing of endothelial cells from mock and infected mice at 2dpi of both age groups (aged: 72–85 weeks; young: 15 weeks) showed substantially lower significant differentially regulated genes in infected aged mice than in young mice (712 versus 2294 genes). Viral recognition and anti-viral pathways such as RIG-I-like receptor signaling, NOD-like receptor signaling and interferon signaling were regulated in response to SARS-CoV-2. Young mice showed several fold higher interferon responses (Ifitm3, Ifit1, Isg15, Stat1) and interferon-induced chemokines (Cxcl10 and Cxcl11) than aged mice. Endothelial cells from infected young mice displayed elevated expression of chemokines (Cxcl9, Ccl2) and leukocyte adhesion markers (Icam1) underscoring that inflammation of lung endothelium during infection could facilitate leukocyte adhesion and thromboinflammation. TREM1 and acute phase response signaling were particularly prominent in endothelial cells from infected young mice. Immunohistochemistry was unable to detect viral protein in pulmonary endothelium. In conclusion, our data demonstrate that the early host response of the endothelium to SARS-CoV-2 infection declines with aging, which could be a potential contributor to disease severity.

Our understanding of the specificities of innate immune protection against viral pathogens in non-model invertebrate species is limited, and comparative immunological approaches may offer opportunities to protect aquaculturally significant species such as abalone, against viral threats. Haliotid herpesvirus (HaHV-1) is a re-emerging viral pathogen of abalone, and has a high mortality rate in the dominant wild and farmed species in Australia, the Australian greenlip abalone (Haliotis laevigata), the blacklip (Haliotis rubra) and a hybrid of the two. To gain a better understanding of the anti-viral immune system counterparts of Australian abalone, gene mining strategies and domain analysis of the recently released H. laevigata draft genome was performed, with comparisons made to the better studied mollusc, the oyster (Crassostrea gigas). Significant divergence in members of the TLR, cytosolic RNA/DNA and RNA interference signalling pathways was observed between the two molluscs, with the oyster more closely reflecting that of the mammalian immune response. Interestingly, a homolog for the anti-viral RNA sensing adaptor protein Mitochondrial anti-viral-signalling protein was absent in H. laevigata, as well as the 4 other abalone protein databases currently available, despite the presence of a RIG-I homolog. Additionally, STING, a member of the dsDNA sensing pathway was absent in H. laevigata, as well as 2 other abalone species, however is present in the oyster genome, and two additional abalone species (Haliotis rufescens, Haliotis discus hannai).This work provides a better understanding of the key features of the abalone anti-viral innate immune signalling system and may provide much needed information towards the development of anti-viral strategies in these animals.

Silke Robatzek, a Heisenberg Professor at Ludwig-Maximilian-University in Munich, Germany, discusses her interest in plant science and her decision to pursue a career in research. She is motivated by her curiosity and a desire to contribute to society through discovering new knowledge. Robatzek also highlights the importance of mentors and role models in her career, and she mentions her favorite papers from the New Phytologist journal. She expresses her fascination with olive trees and their genetic diversity in terms of plant immunity. [Extracted from the article]

We previously showed that several polymorphisms in genes encoding pattern recognition receptors that cause amino acid substitutions alter pathogen recognition ability and disease susceptibility in pigs. In this study, we expanded our analysis to a wide range of immune-related genes and investigated polymorphism distribution and its influence on pneumonia in multiple commercial pig populations. Among the polymorphisms in 42 genes causing 634 amino acid substitutions extracted from the swine genome database, 80 in 24 genes were found to have a minor allele frequency of at least 10% in Japanese breeding stock pigs via targeted resequencing. Of these, 62 single nucleotide polymorphisms (SNPs) in 23 genes were successfully genotyped in 862 pigs belonging to four populations with data on pneumonia severity. Association analysis using a generalized linear mixed model revealed that 12 SNPs in nine genes were associated with pneumonia severity. In particular, SNPs in the cellular receptor for immunoglobulin G FCGR2B and the intracellular nucleic acid sensors IFI16 and LRRFIP1 were found to be associated with mycoplasmal pneumonia of swine or porcine pleuropneumonia in multiple populations and may therefore have wide applications in the improvement of disease resistance in pigs. Functional analyses at the cellular and animal levels are required to clarify the mechanisms underlying the effects of these SNPs on disease susceptibility.

Fibrinogen-related proteins (FREPs) are calcium-dependent lectins with one fibrinogen domain and one or two immunoglobulin-like domains. The FREPs of gastropod molluscs can undergo somatic diversification, which is unique among pathogen-recognizing molecules of invertebrates. The structure of the genomic regions encoding FREPs implies the possibility of alternative splicing and somatic mutagenesis. Since the discovery of FREPs in Biomphalaria glabrata, these molecules have been described in many gastropods. At least 14 subfamilies of FREPs are currently known. FREPs of different subfamilies selectively participate in the immune response to various pathogens. In particular, their role in defense reactions to trematode invasion and resistance to trematodes of particular species has been confirmed. The supposed functions of FREPs are diverse, ranging from the recognition of foreign matter to the opsonization and neutralization of pathogens. Despite the abundance of studies of FREPs, the Russian literature on this subject is scarce. The main purpose of this review is to analyze the available information on gastropod FREPs and to discuss their role among pattern recognition receptors of molluscs. [ABSTRACT FROM AUTHOR]

Objective: Eosinophils are one of the least abundant leukocytes in blood circulation; however, they compensate for this sparsity by highly potent content of their granules. Their involvement in numerous pathological conditions including acute and chronic infections make them an interesting research area for the field of immunology. Eosinophils play critical roles in the maintenance of immune homeostasis through their effector and modulatory functions in shaping innate and adaptive responses. Although they are mainly known for their roles in parasitic infections, it has become increasingly clear that eosinophils function not only in fungal, bacterial and viral infections, but also in tissue repair and signaling pathways regulating mast cells, Th2 and B cells. Of all the mediators of innate immunity, pattern recognition receptors (PRRs) are of great importance in the context of the stimuli. Therefore, we analyzed and cross-checked mRNA expression profiles of membrane-bound and cytosolic PRRs by comparing EoL-1 and HL-60 human eosinophil like cell lines to human primary eosinophils in silico. Materials and Methods: Utilizing publicly available databases, we analyzed PRR repertoires of eosinophils to determine the most ideal cell line models for in vitro mechanistic studies, requiring high protein and mRNA yields. Results: Our findings revealed that toll-like receptors 2 and NOD-like receptor 3 (NLRP3) had higher basal expressions in both cell lines than human primary eosinophils as opposed to NLRP12, laboratory of genetics and physiology 2 (LGP2), Dectin-1, whose expressions were higher in primary eosinophils than in both cell lines. Conclusion: These data might attribute new physiological functions to these receptors of NLR, RIG-I like receptor and C-type lectin receptor families in eosinophil immunity. [ABSTRACT FROM AUTHOR]

Recognition of viruses invading the central nervous system (CNS) by pattern recognition receptors (PRRs) is crucial to elicit early innate responses that stem dissemination. These innate responses comprise both type I interferon (IFN-I)-mediated defenses as well as signals recruiting leukocytes to control the infection. Focusing on insights from the neurotropic mouse CoV model, this review discusses how early IFN-I, fibroblast, and myeloid signals can influence protective anti-viral adaptive responses. Emphasis is placed on three main areas: the importance of coordinating the distinct capacities of resident CNS cells to induce and respond to IFN-I, the effects of select IFN-stimulated genes (ISGs) on host immune responses versus viral control, and the contribution of fibroblast activation and myeloid cells in aiding the access of T cells to the parenchyma. By unraveling how the dysregulation of early innate components influences adaptive immunity and viral control, this review illustrates the combined effort of resident CNS cells to achieve viral control. [ABSTRACT FROM AUTHOR]

Dermatophytosis is a common superficial infection caused by dermatophytes, a group of pathogenic keratinophilic fungi. Apart from invasion against skin barrier, host immune responses to dermatophytes could also lead to pathologic inflammation and tissue damage to some extent. Therefore, it is of great help to understand the pathogenesis of dermatophytes, including fungal virulence factors and anti-pathogen immune responses. This review aims to summarize the recent advances in host-fungal interactions, focusing on the mechanisms of anti-fungal immunity and the relationship between immune deficiency and chronic dermatophytosis, in order to facilitate novel diagnostic and therapeutic approaches to improve the outcomes of these patients. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a significant global health challenge, claiming the lives of up to 1.5 million individuals annually. TB is caused by the human pathogen Mycobacterium tuberculosis (Mtb), which primarily infects innate immune cells in the lungs. These immune cells play a critical role in the host defense against Mtb infection, influencing the inflammatory environment in the lungs, and facilitating the development of adaptive immunity. However, Mtb exploits and manipulates innate immune cells, using them as favorable niche for replication. Unfortunately, our understanding of the early interactions between Mtb and innate effector cells remains limited. This review underscores the interactions between Mtb and various innate immune cells, such as macrophages, dendritic cells, granulocytes, NK cells, innate lymphocytes-iNKT and ILCs. In addition, the contribution of alveolar epithelial cell and endothelial cells that constitutes the mucosal barrier in TB immunity will be discussed. Gaining insights into the early cellular basis of immune reactions to Mtb infection is crucial for our understanding of Mtb resistance and disease tolerance mechanisms. We argue that a better understanding of the early host-pathogen interactions could inform on future vaccination approaches and devise intervention strategies. [ABSTRACT FROM AUTHOR]

Background: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease of unknown etiology. Researchers have recently drawn attention to the possible role of viruses in the development of IBS and provided evidence in this regard. In this study, it was decided to investigate the possible role of rotavirus infection in the onset of IBS. Methods: Stool and serum samples were collected from 40 patients with IBS and 40 healthy individuals. To evaluate the previous exposure to rotavirus we checked the presence and concentration of anti-rotavirus IgG by ELISA. ELISA test was performed on the serum samples. A real-time polymerase chain reaction (PCR) test was also used to measure the viral load in the stool. Finally, the data were analyzed by SPSS version 22 software. Results: No significant relationship was found between anti-rotavirus IgG presence and its level in the serum of case and healthy individuals (P value>0.05). Moreover, there was no significant difference between the viral genome load in the stool samples of the two groups (P value>0.05). Conclusion: According to the results, it seems unlikely that a link exists between rotavirus infection and the onset of IBS, but the possible role of other gastrointestinal viruses, including coronavirus, remains. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a key role in host health and disease, particularly through their interactions with the immune system. Intestinal homeostasis is dependent on the symbiotic relationships between the host and the diverse gut microbiota, which is influenced by the highly co-evolved immune–microbiota interactions. The first step of the interaction between the host and the gut microbiota is the sensing of the gut microbes by the host immune system. In this review, we describe the cells of the host immune system and the proteins that sense the components and metabolites of the gut microbes. We further highlight the essential roles of pattern recognition receptors (PRRs), the G protein-coupled receptors (GPCRs), aryl hydrocarbon receptor (AHR) and the nuclear receptors expressed in the intestinal epithelial cells (IECs) and the intestine-resident immune cells. We also discuss the mechanisms by which the disruption of microbial sensing because of genetic or environmental factors causes human diseases such as the inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR]

The innate immune system is critical for inducing durable and protective T cell responses to infection and has been increasingly recognized as a target for cancer immunotherapy. In this review, we present a framework wherein distinct innate immune signaling pathways activate five key dendritic cell activities that are important for T cell-mediated immunity. We discuss molecular pathways that can agonize these activities and highlight that no single pathway can agonize all activities needed for durable immunity. The immunological distinctions between innate immunotherapy administration to the tumor microenvironment versus administration via vaccination are examined, with particular focus on the strategies that enhance dendritic cell migration, interferon expression, and interleukin-1 family cytokine production. In this context, we argue for the importance of appreciating necessity vs. sufficiency when considering the impact of innate immune signaling in inflammation and protective immunity and offer a conceptual guideline for the development of efficacious cancer immunotherapies. Innate immune pathways are commonly discussed targets of cancer immunotherapy. Cao and Kagan review the state of this rapidly advancing field of study. They introduce the concept that five key innate immune activities in dendritic cells are needed to stimulate durable T cell-mediated anti-tumor immunity. [ABSTRACT FROM AUTHOR]

It is essential to overcome the challenges of structural complexity, synthesis, source heterogeneity, and lack of analytical tools, to elucidate the molecular mechanisms of carbohydrate-based adjuvants for the design of new putative vaccines. The physicochemical factors of carbohydrates, including molecular weight, monosaccharide composition, functional groups, and spatial conformation, determine their recognition by pattern recognition receptors, consequently affecting their immunomodulatory activities. Carbohydrate-based adjuvants may harbor advantages in the regulation of antigen transport, presentation, and processing, thus enriching the type of adaptive immunity that can be initiated. Advanced chemical and computational technologies can provide new tools for the development of carbohydrate-based adjuvants. By increasing our efforts to elucidate the immunomodulatory mechanisms of carbohydrates, especially those representing or mimicking microbial infections, we might provide new biological evidence and engineering perspectives for the design of next-generation vaccine adjuvants. Adjuvants are essential components of modern vaccines. One general mechanism underlying their immunostimulatory functions is the activation of pattern recognition receptors (PRRs) of innate immune cells. Carbohydrates – as essential signaling molecules on microbial surfaces – are potent PRR agonists and candidate materials for adjuvant design. Here, we summarize the latest trends in developing carbohydrate-containing adjuvants, with fresh opinions on how the physicochemical characteristics of the glycans (e.g., molecular size, assembly status, monosaccharide components, and functional group patterns) affect their adjuvant activities in aiding antigen transport, regulating antigen processing, and enhancing adaptive immune responses. From a translational perspective, we also discuss potential technologies for solving long-lasting challenges in carbohydrate adjuvant design. [ABSTRACT FROM AUTHOR]

Understanding the molecular mechanisms of atherosclerotic vascular lesions formation is necessary both for assessing the risks of cardiovascular diseases and for finding approaches to their therapy. The task remains relevant, despite the large number of studies carried out, because there are differences in the factors of genetic predisposition to atherosclerosis and its complications between different ethno-territorial groups. The aim of this study was to search for genetic variants of pattern recognition receptors associated with lipid metabolism disorders that can lead to the development of coronary atherosclerosis (CA).Material and methods. Analysis of exons and adjacent splicing sites of pattern recognition receptors genes in patients with CA (30 men), and then genotyping of a population sample from Novosibirsk (n = 1441) by real-time PCR for selected rs113706342 of the TLR1 gene and analysis of associations of its carriage with lipid metabolism were performed.Results and discussion. The frequency of the minor allele rs113706342 C of the TLR1 gene in the sample of residents of Novosibirsk was 0.0114 ± 0.0062, the carriage of this variant was associated with an increased level of low-density lipoprotein cholesterol in both women and men (p = 0.009 and p = 0.019, respectively). Women carriers of the minor allele C for rs113706342 also had a statistically significant increase in total serum cholesterol (p = 0.013) compared with TT homozygotes. To test the role of this variant in the development of CA, genotyping of an extended sample of patients is required. In one of the patients with CA, a previously undescribed single nucleotide variant chr16:3614637 G/C was found, leading to the Leu101Val substitution in the NLRC3 gene; segregation analysis is required to assess its functional significance.Conclusions. The association of rs113706342 C of the TLR1 gene with lipid metabolism disorders in the Russian population is shown.

Abstract Neurological disorders such as stroke, multiple sclerosis, as well as the neurodegenerative diseases Parkinson's or Alzheimer's disease are accompanied or even powered by danger associated molecular patterns (DAMPs), defined as endogenous molecules released from stressed or damaged tissue. Besides protein-related DAMPs or “alarmins”, numerous nucleic acid DAMPs exist in body fluids, such as cell-free nuclear and mitochondrial DNA as well as different species of extracellular RNA, collectively termed as self-extracellular nucleic acids (SENAs). Among these, microRNA, long non-coding RNAs, circular RNAs and extracellular ribosomal RNA constitute the majority of RNA-based DAMPs. Upon tissue injury, necrosis or apoptosis, such SENAs are released from neuronal, immune and other cells predominantly in association with extracellular vesicles and may be translocated to target cells where they can induce intracellular regulatory pathways in gene transcription and translation. The majority of SENA-induced signaling reactions in the brain appear to be related to neuroinflammatory processes, often causally associated with the onset or progression of the respective disease. In this review, the impact of the diverse types of SENAs on neuroinflammatory and neurodegenerative diseases will be discussed. Based on the accumulating knowledge in this field, several specific antagonistic approaches are presented that could serve as therapeutic interventions to lower the pathological outcome of the indicated brain disorders.

C-type lectins in organisms play an important role in the process of innate immunity. In this study, a C-type lectin belonging to the DC-SIGN class of Micropterus salmoides was identified. MsDC-SIGN is classified as a type II transmembrane protein. The extracellular segment of MsDC-SIGN possesses a coiled-coil region and a carbohydrate recognition domain (CRD). The key amino acid motifs of the extracellular CRD of MsDC-SIGN in Ca2+-binding site 2 were EPN (Glu-Pro-Asn) and WYD (Trp-Tyr-Asp). MsDC-SIGN-CRD can bind to four pathogen-associated molecular patterns (PAMPs), including lipopolysaccharide (LPS), glucan, peptidoglycan (PGN), and mannan. Moreover, it can also bind to Gram-positive, Gram-negative bacteria, and fungi. Its CRD can agglutinate microbes and displays D-mannose and D-galactose binding specificity. MsDC-SIGN was distributed in seven tissues of the largemouth bass, among which the highest expression was observed in the liver, followed by the spleen and intestine. Additionally, MsDC-SIGN was present on the membrane of M. salmoides leukocytes, thereby augmenting the phagocytic activity against bacteria. In a subsequent investigation, the expression patterns of the MsDC-SIGN gene and key genes associated with the TLR signaling pathway (TLR4, NF-κB, and IL10) exhibited an up-regulated expression response to the stimulation of Aeromonas hydrophila. Furthermore, through RNA interference of MsDC-SIGN, the expression level of the DC-SIGN signaling pathway-related gene (RAF1) and key genes associated with the TLR signaling pathway (TLR4, NF-κB, and IL10) was decreased. Therefore, MsDC-SIGN plays a pivotal role in the immune defense against A. hydrophila by modulating the TLR signaling pathway.