Search

In innate immunity, the first layer of defense against any microbial infection is triggered by the perception of pathogen-associated molecular patterns by highly specific pattern recognition receptors. The Pseudomonas syringae pv. tomato and Pseudomonas aeruginosa are plant-pathogenic bacterial species that include pathogenic strains in a wide range of different plant species. In the current study, extensive analysis including gene expression of 12 hub genes, gene ontology, protein–protein interaction, and cis-element prediction to dissect the Arabidopsis response to above-mentioned bacteria were performed. Further, we evaluated weighted co-expression network analysis (WGCNA) in the wild-type plants and coi-1 mutant line and determined changes in responsive genes at two time-points (4 and 8 h) of post-treatment with P. syringae and P. aeruginosa. Compared to the wild-type plants, coi-1 mutant showed significant expression in most of the genes involved, indicating that their protein products have important role in innate immunity and RNA silencing pathways. Our findings showed that 12 hub genes were co-expressed in response to P. syringae and P. aeruginosa infections. Based on the network analysis, transcription factors, receptors, protein kinase, and pathogenesis-related protein (PR1) were involved in the immunity system. Gene ontology related to each module was involved in defense response, protein serine kinase activity, and primary miRNA processing. Based on the cis-elements prediction, MYB, MYC, WRE3, W-box, STRE, and ARE contained the most number of cis-elements in co-expressed network genes. Also, in coi-1 mutant, most responsive genes against theses pathogens were up-regulated. The knowledge gained in the gene expression analysis in response to P. syringae and P. aeruginosa in the model plant, i.e., Arabidopsis, is essential to allow us to gain more insight about the innate immunity in other crops. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) and M-ficolin are the pattern recognition proteins of the innate immune system. In this report, a mixture of CRP and M-ficolin reversibly co-aggregated in a calcium-dependent manner. This coaggregation was enhanced at low pH (6.5) or low salt (35 mM NaCl) concentrations. The co-aggregate was dissolved by adding EDTA and reformed by adding calcium. The M-ficolin fibrinogen-like domain (FD1), the ligand-binding domain of M-ficolin, also showed calcium-dependent coaggregation with CRP, indicating that reversible coaggregation is caused by CRP interacting with FD1. Interestingly, adding phosphocholine (PC), the ligand of CRP, to a CRP-FD1 mixture abolished the reversible coaggregation activity. PC also inhibited the interaction between CRP and FD1. These results indicate that CRP retains PC-binding activity in the coaggregation state and that FD1 binds specifically to the PC-binding site on CRP but does not fully occupy the five PC-binding sites on a CRP pentamer as judged by SDS-PAGE analysis of precipitates. Coaggregation analysis using FD1 mutants showed that FD1 also retains ligand-binding activity in the coaggregation state and that coaggregation requires the trimeric form of FD1. It was also found that modifications to the ligand-binding site of FD1 affect coaggregation efficiency. Although the biological functions of the coaggregation activity of CRP and M-ficolin remain unresolved, the co-aggregates may function as bacteria-trapping particles with affinities for ligands of CRP and M-ficolin. In addition, coaggregation may be involved in CRP deposition in the lesions of several arterial diseases, such as atherosclerosis. • CRP and M-ficolin co-aggregate depending on calcium. • Reduced pH or salt-concentration enhances the coaggregation activity. • Both proteins retain their ligand-binding activity in co-aggregates. • Co-aggregates may act as bacteria-trapping particles under acidosis conditions. • Coaggregation may be involved in CRP deposition in the lesions of atherosclerosis. [ABSTRACT FROM AUTHOR]

The environmental conditions and isolation in the Antarctic have driven the evolution of a unique biodiversity at a macro to microorganism scale. Here, we investigated the possible adaptation of the teleost Nototheniacoriiceps immune system to the cold environment and unique microbial community of the Southern Ocean. The fish immune system was stimulated through an intraperitoneal injection of lipopolysaccharide (LPS 0111:B4 from E. coli) and the tissue transcriptomic response and plasma biochemistry were analyzed 7 days later and compared to a sham injected control. Gene transcription in the head-kidney, intestine and skin was significantly modified by LPS, although tissues showed different responsiveness, with the duodenum most modified and the skin the least modified. The most modified processes in head-kidney, duodenum and skin were related to cell metabolism (up-regulated) and the immune system (comprising 30% of differentially expressed genes). The immune processes identified were mostly down-regulated, particularly interleukins and pattern recognition receptors (PRRs), nucleotide-binding oligomerization domain-like receptors and mannose receptors, unlike the toll-like receptors response commonly described in other teleost fish. The modified transcriptional response was not mirrored by a modified systemic response, as the circulating levels of enzymes of innate immunity, lysozyme and antiproteases, were not significantly different from the untreated and sham control fish. In conclusion, while the N.coriiceps immune system shares many features with other teleosts there are also some specificities. Further studies should better characterize the PRRs and their role in Antarctic teleosts, as well as the importance of the LPS source and its consequences for immune activation in teleosts. [ABSTRACT FROM AUTHOR]

Numerous cardiovascular disorders have atherosclerosis as their pathological underpinning. Numerous studies have demonstrated that, with the aid of pattern recognition receptors, cytokines, and immunoglobulins, innate immunity, represented by monocytes/macrophages, and adaptive immunity, primarily T/B cells, play a critical role in controlling inflammation and abnormal lipid metabolism in atherosclerosis. Additionally, the finding of numerous complement components in atherosclerotic plaques suggests yet again how heavily the immune system controls atherosclerosis. Therefore, it is essential to have a thorough grasp of how the immune system contributes to atherosclerosis. The specific molecular mechanisms involved in the activation of immune cells and immune molecules in atherosclerosis, the controversy surrounding some immune cells in atherosclerosis, and the limitations of extrapolating from relevant animal models to humans were all carefully reviewed in this review from the three perspectives of innate immunity, adaptive immunity, and complement system. This could provide fresh possibilities for atherosclerosis research and treatment in the future. [ABSTRACT FROM AUTHOR]

The initial defense against invading pathogenic microbes is the activation of innate immunity by binding of pattern recognition receptors (PRRs) to pathogen associated molecular patterns (PAMPs). To explain the action of PRRs from hagfish, one of the extant jawless vertebrates , we purified the GlcNAc recognition complex (GRC) from serum using GlcNAc-agarose. The GRC comprises four proteins of varying molecular masses: 19 kDa, 26 kDa, 27 kDa, and 31 kDa. Exposure of Escherichia coli to the GRC led to the phagocytic activation of macrophages, revealing the opsonic function of the GRC. The GRC in serum formed a large complex with a molecular mass of approximately 1200 kDa. The GRC bound to Escherichia coli but not to rabbit red blood cells, despite both having GlcNAc on their surface. These structural and binding properties are similar to those of mannose-binding lectin (MBL). The amino acid sequence of a portion of the 31 kDa protein in the GRC matched the amino acid sequence of variable lymphocyte receptor (VLR)-B in some place. According to the Western blot analysis, the 31 kDa protein was recognized by the anti-hagfish VLR-B antiserum. Based on the results, it appears that the GRC functions as a PRR like MBL and that its 31 kDa protein has a structure similar to that of VLR-B. • GlcNAc recognition complex (GRC) in hagfish serum acted as an opsonin. • The GRC acted as a pattern recognition receptor. • The 31 kDa protein in the GRC had the similar structure to VLR-B. [ABSTRACT FROM AUTHOR]

At the end of December 2019, the COVID-19 pandemic began in Wuhan of China. COVID-19 affects different people with a wide spectrum of clinical manifestations, ranging from asymptomatic with recovery without hospitalization up to a severe acute respiratory syndrome (SARS). The innate and adaptive immunity appears responsible for the defense against the virus and recovery from the disease. The innate immune system, as the first line of defense, is essential for the detection of virus and subsequent activation of acquired immunity. The innate immune response is carried out by sentinel cells such as monocytes/macrophages and dendritic cells and by receptors known as pattern recognition receptors (PRR). These receptors can recognize various components of the virus, which lead to intracellular signaling and subsequently the synthesis of various cytokines. These cytokines then recruit other immune cells, activate adaptive immune responses, and inhibit viral spreading. The most common receptors include Toll-like receptors, C-type lectin receptors, and RIG-I like receptors. This review describes the current knowledge about the interplay between innate immune responses and SARS-CoV-2 with a focus on the innate immune cells and the role of their receptors in viral RNA recognition, as well as their mechanisms for recognizing SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The intestinal tract harbors a diverse community of microbes that have co-evolved with the host immune system. Although many of these microbes execute functions that are critical for host physiology, the host immune system must control the microbial community so that the dynamics of this interdependent relationship is maintained. To facilitate host homeostasis, the immune system ensures that the microbial load is tolerated, but anatomically contained, while remaining reactive to microbial invasion. Although the microbiota is required for intestinal immune development, immune responses regulate the structure and composition of the intestinal microbiota by evolving unique immune adaptations that manage this high-bacterial load. The immune mechanisms work together to ensure that commensal bacteria rarely breach the intestinal barrier and that any that do invade should be killed rapidly to prevent penetration to systemic sites. The communication between microbiota and the immune system is mediated by the interaction of bacterial components with pattern recognition receptors expressed by intestinal epithelium and various antigen-presenting cells resulting in activation of both innate and adaptive immune responses. Interaction between the microbial community and host plays a crucial role in the mucosal homeostasis and health status of the host. In addition to providing a home to numerous microbial inhabitants, the intestinal tract is an active immunological organ, with more resident immune cells than anywhere else in the body, organized in lymphoid structures called Peyer’s patches and isolated lymphoid follicles such as the cecal tonsils. Macrophages, dendritic cells, various subsets of T cells, B cells and the secretory immunoglobulin A (IgA) they produce, all contribute to the generation of a proper immune response to invading pathogens while keeping the resident microbial community in check without generating an overt inflammatory response to it. IgA-producing plasma cells, intraepithelial lymphocytes, and gdT cell receptor-expressing T cells are lymphocytes that are uniquely present in the mucosa. In addition, of the gdT cells in the intestinal lamina propria, there are significant numbers of IL-17-producing T cells and regulatory T cells. The accumulation and function of these mucosal leukocytes are regulated by the presence of intestinal microbiota, which regulate these immune cells and enhance the mucosal barrier function allowing the host to mount robust immune responses against invading pathogens, and simultaneously maintains immune homeostasis. [ABSTRACT FROM AUTHOR]

Understanding the molecular drivers and feedback loops of osteoarthritis (OA) may provide future therapeutic strategies to modulate the disease progression. The current paradigm of OA is evolving from a purely mechanical disease caused by cartilage wear toward a complex biological response connecting biomechanics, inflammation, and the immune system. The view of OA as a chronic wound highlights the role inflammation plays and also the body's attempts to repair an ongoing injury. Inflammatory signals, including cytokines such as interleukin‐1 and tissue necrosis factor α, surface‐expressed pattern recognition receptors such as toll‐like receptors 2 and 4, complement factors such as C5, as well as pathogen‐associated molecular patterns and damage‐associated molecular patterns drive the enzymatic cascade that degrades cartilage matrix in OA. Considering the joint as an entire organ, interactions between the cells that reside in the synovium including macrophages and other immune cells, appear to drive enzymatic activity in cartilage, which, in turn, feeds signals back to the synovium that continues stimulating degradation in a feed‐forward loop. This review will explore the potential roles of immune cells such as macrophages and T cells in the synovium in both stimulating and modulating the inflammatory response in OA. © 2019 Orthopedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:253‐257, 2020 [ABSTRACT FROM AUTHOR]

Purpose: NOD1 and NOD2 (nucleotide-binding oligomerization domain)—receptors are intracellular receptors and belong to the family of pattern recognition receptors being present in both human and murine renal tubular cells. Besides, NOD1 has been proved to promote apoptosis, upon its overexpression. Hence, we aimed to investigate NOD1 and NOD2 expression in human clear cell renal cell carcinoma (ccRCC). Methods: Tumor and corresponding adjacent healthy tissues from 41 patients with histopathological diagnosis of ccRCC as well as primary isolated renal tubular epithelial cells (TECs) and tumor tissue from a murine xenograft model using CAKI-1 ccRCC cells were analyzed. Results: NOD1 and NOD2 mRNA was constitutively expressed in both tumor and adjacent healthy renal tissue, with NOD1 being significantly lower and in contrast NOD2 significantly higher expressed in tumor tissue compared to healthy tissues. Immunohistochemically, NOD1 was located not only in the cytoplasm, but also in the nucleus in ccRCC tissue whereas NOD2 was solely localized in the cytoplasm in both human ccRCC as well as in the healthy tubular system. Focusing on the vasculature, NOD2 displayed broader expression than NOD1. In primary TECs as well as CAKI-1 cells NOD1 and NOD2 was constitutively expressed and increasable upon LPS stimulation. In the mouse xenograft model, human NOD1 mRNA was significantly higher expressed compared to NOD2. In contrast hereto, we observed a shift towards lower mouse NOD1 compared to NOD2 mRNA expression. Conclusion: In view of reduced apoptosis-associated NOD1 expression in ccRCC tissue opposed to higher expression of NOD2 in tumor vasculature, inducibility of NOD expression in TECs as well as the detected shift of NOD1 and NOD2 expression in the mouse xenograft model, modulation of NOD receptors might, therefore, provide a molecular therapeutic approach in ccRCC. [ABSTRACT FROM AUTHOR]

[Display omitted] Invasive fungal infection is an under recognized and emerging global health threat. Recently, the World Health Organization (WHO) released the first ever list of health-threatening fungi to guide research and public health interventions to strengthen global response to fungi infections and antifungal resistance. Currently, antifungal drugs only demonstrate partial success in improving prognosis of infected patients, and this is compounded by the rapid evolution of drug resistance among fungi species. The increased prevalence of fungal infections in individuals with underlying immunological deficiencies reflects the importance of an intact host immune system in controlling mycoses, and further highlights immunomodulation as a potential new avenue for the treatment of disseminated fungal diseases. In this review, we will summarize how host innate immune cells sense invading fungi through their pattern recognition receptors, and subsequently initiate a series of effector mechanisms and adaptive immune responses to mediate fungal clearance. In addition, we will discuss emerging preclinical and clinical data on antifungal immunotherapies and fungal vaccines which can potentially expand our antifungal armamentarium in future. [ABSTRACT FROM AUTHOR]

In the host innate immune system, various pattern recognition receptors (PRRs) recognize conserved pathogens-associated molecular patterns (PAMPs), and represent an efficient first line of defense against invading pathogens. TLR22 is one of the fish-specific Toll-like receptors (TLRs), identified in a variety of fish species. In this study, we report the cloning and identification of a TLR22 cDNA from the gills of common carp ( Cyprinus carpio L.). The full-length CcTLR22 cDNA was 3301 bp long, including a 32 bp 5'-untranslated region (UTR), an open reading frame (ORF) of 2838 bp and a 432 bp 3′-UTR.The CcTLR22 protein was found to comprise a signal peptide, 16 LRR domains, a LRRCT domain in the extracellular region and a TIR domain in the cytoplasmic region, which fits with the characteristic TLR domain architecture. The genomic organization of CcTLR22 was identified, which was encoded by an uninterrupted exon. Sequence alignment and phylogenetic analysis showed that all known teleost TLR22 members were clustered into an independent clade of the TLR22 family, and showed high amino acid identities with other fish TLRs. Real-time PCR assay showed that CcTLR22 mRNA was expressed in almost all tissues examined, while the levels obviously varied among different tissues. When challenged with poly(I:C) (a viral model) or A. hydrophila bacteria, the expression level of CcTLR22 was up-regulated in a variety of common carp tissues. These results indicate that CcTLR22 plays a significant role in systemic as well as mucosal defence after viral or bacterial stimulation or infection. [ABSTRACT FROM AUTHOR]

The innate immune system relies on families of pattern recognition receptors (PRRs) that detect distinct conserved molecular motifs from microbes to initiate antimicrobial responses. Activation of PRRs triggers a series of signaling cascades, leading to the release of pro-inflammatory cytokines, chemokines and antimicrobials, thereby contributing to the early host defense against microbes and regulating adaptive immunity. Additionally, PRRs can detect perturbation of cellular homeostasis caused by pathogens and fine-tune the immune responses. Among PRRs, nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) have attracted particular interest in the context of cellular stress-induced inflammation during infection. Recently, mechanistic insights into the monitoring of cellular homeostasis perturbation by NLRs have been provided. We summarize the current knowledge about the disruption of cellular homeostasis by pathogens and focus on NLRs as innate immune sensors for its detection. We highlight the mechanisms employed by various pathogens to elicit cytoskeleton disruption, organelle stress as well as protein translation block, point out exemplary NLRs that guard cellular homeostasis during infection and introduce the concept of stress-associated molecular patterns (SAMPs). We postulate that integration of information about microbial patterns, danger signals, and SAMPs enables the innate immune system with adequate plasticity and precision in elaborating responses to microbes of variable virulence. [ABSTRACT FROM AUTHOR]

In the immune system, C-type lectins, as pattern recognition receptors, have an important function. Carbohydrate-recognition domains (CRDs) endow C-type lectins with the function of recognizing and scavenging non-self factors. In the present study, a new C-type lectin (designated as PtCTL-9 according to the order of discovery) from swimming crab (Portunus trituberculatus) was characterized. QPN (Gln-Pro-Asn) and FHS (Phe-His-Ser) were identified as the key motifs that determine carbohydrate binding. Motif QPN was mutated to QPD (Gln-Pro-Asp) (M1) and EPN (Glu-Pro-Asn) (M2) to study its immune function and for comparative analysis. The results showed that PtCTL-9 displayed broad non-self immunity. PtCTL-9 could also function as an opsonin to promote phagocytosis and the in vitro encapsulation of hemocytes. These results indicated that PtCTL-9 has an extensive nonself-recognition ability, regulates pathogen clearance, and its QPN motif is important in PtCTL-9's immune function. • A C-type lectin PtCTL-9 with a novel QPN motif was identified from Portunus trituberculatus. • PtCTL-9 possessed strong binding activity to nonself particles while its two mutants displayed weak binding activity. • PtCTL-9 inhibited the growth of S. cerevisiae. • PtCTL-9 promoted phagocytosis and encapsulation activity of hemocytes in vitro. [ABSTRACT FROM AUTHOR]

The innate immune system identifies exogenous threats or endogenous stress through germline-encoded receptors called pattern recognition receptors (PRRs) that initiate consecutive downstream signaling pathways to control immune responses. However, the contribution of the immune system and inflammation to fibrosing interstitial lung diseases (ILD) remains poorly understood. Immunoreceptor tyrosine-based motif-bearing C-type lectin-like receptors (CTLRs) may interact with various immune cells during tissue injury and wound repair processes. Dectin-1 is a CTLR with dominant mechanisms manifested through its intracellular signaling cascades, which regulate fibrosis-promoting properties through gene transcription and cytokine activation. Additionally, immune impairment in ILD facilitates microbiome colonization; hence, Dectin-1 is the master protector in host pulmonary defense against fungal invasion. Recent progress in determining the signaling pathways that control the balance of fibrosis has implicated immunoreceptor tyrosine-based motif-bearing CTLRs as being involved, either directly or indirectly, in the pathogenesis of fibrosing ILD. [ABSTRACT FROM AUTHOR]

The innate immune system is the first line of defense protecting the hosts against invading pathogens. Mud crab (Scylla paramamosain) is widely distributed in China and Indo-west Pacific countries, which develops a very complicated innate immune system against pathogen invasions. Innate immunity involves the humoral and cellular responses that are linked to the pattern recognition receptors (PRRs). PRRs initially recognize the infection and trigger the activation of signaling cascades, leading to transcriptional regulation of inflammatory mediators that function in pathogenic control and clearance. In mud crab S. paramamosain , the Toll/Toll-like receptors, lipopolysaccharide and β-1,3-glucan binding proteins, C-type lectins, scavenger receptors, and down syndrome cell adhesion molecules have been identified as receptor families responsible for the recognition of bacteria, fungi, and viruses, and are important components in the innate immune system. In this review, we summarize the literature on the current knowledge and the roles of PRRs in the immune defenses of mud crab, which in an effort to provide much information for further researches. • Five pattern recognition receptors (PRRs) have been reported in mud crab. • Different PRRs target to different ligands in the innate immunity. • PRRs activate the intracellular signaling cascades and subsequently respond to the infections. [ABSTRACT FROM AUTHOR]