查看更多>>摘要：Aflatoxin B1 (AFB1) is a mycotoxin with strong toxicity and play a large proportion in aspergillosis. Heterophil extracellular traps (HETs) was considered as an innate immune response of chickens to resist pathogens. AFB1 has been reported to trigger macrophages extracellular traps (METs) in THP-1 cells and RAW264.7 cells, but whether AFB1 could also activate HETs release, and the mechanism underlying AFB1-activated HETs in chicken remains unclear. In this study, we confirmed that AFB1 could induce HETs release, which was a network of DNA-based structures consist of citrullinated histone 3 (citH3) and elastase. Meanwhile, AFB1-activated HETs rely on the glycolytic process to provide energy, NADPH oxidase and p38 signaling pathway. Moreover, it has been verified that AFB1-activated HETs release could significantly increase the biochemical indexes of liver (ALT and AST) and kidney (CRE and BUN) in serum. In addition, histopathological observation showed that AFB1 caused swelling, necrosis and vacuolation of hepatocytes in liver, and necrosis, exfoliated of nephrocyte in kidney. Further investigation demonstrated that AFB1 significantly decreased the levels of SOD and GSH-PX but increased the level of MDA, and meanwhile induced the mRNA expressions of TNF-alpha, IL-6 and IL-1 beta, iNOS, COX-2, NLRP3, caspase-1, caspase-3 and caspase-11. However, all these AFB1-induced biochemical indexes and histopathological changes were effectively alleviated by DNase I (the standard degradant for HETs). In conclusion, it has preliminary confirmed that AFB1-activated HETs formation contributed to the immunotoxicity in chicken and provide new strategies for the therapy in aspergillosis.
查看更多>>摘要：Down syndrome cell adhesion molecule (Dscam), also called hypervariable Dscam (Dscam-hv), is an important player in arthropod alternative splicing that connects neurons and immune regulation, acting as a pathogen specific recognition molecule. Dscam-hv has two forms: transmembrane (TM) Dscam (mDscam) and soluble Dscam (sDscam). Herein, we investigated two transmembrane variants of mDscam resulting from alternative splicing of the transmembrane domain, focusing on differences in their immune regulation. We characterized the Dscam[TM1] and Dscam[TM2] genes of Chinese mitten crab (Eriocheir sinensis) through bioinformatics analysis. Both genes are expressed in the gill, intestine, and other immune tissues. Following gram-positive and gram negative bacteria stimulation, EsDscam[TM1] and EsDscam[TM2] mRNA expression levels increased significantly in hemocytes. Sequencing showed that EsDscam[TM1] was more abundant in hemocytes than EsDscam [TM2]. Additionally, the two subtypes differ in their regulation of antimicrobial peptides, the proportion of exon 33 carried, and bacterial phagocytosis.
查看更多>>摘要：Pigs are important domestic livestock and a comprehensive understanding of their immune system is critical to improve swine vaccine efficacy. Pig models represent an excellent animal model for immunological studies because of their anatomical and physiological similarities to humans. A significant portion of pig immunological studies focused on characterizing the conventional T cell (Tconv) immune responses. These cells recognize peptides presented by major histocompatibility complex (MHC) proteins. In contrast, unconventional T cells are non-MHC-restricted and profoundly regulate conventional T cells. Key subsets of unconventional T cells reviewed here include natural killer T (NKT) cells, gamma delta T cells, mucosal-associated invariant T (MAIT) cells, intraepithelial lymphocytes (IELs), and two potential unconventional T cell subsets expressing NKp46 or CD11b. Unlike Tconvs, most of these cells recognize lipids, small molecule metabolites, or modified peptides, and they generally show simplified patterns of T cell receptor (TCR) expression and rapid effector responses. Here, we review that unconventional T cells are an abundant and critical component of the porcine immune system, summarize the current understanding of these cells, and highlight some of the key differences among mouse, human, and porcine unconventional T cells.
Mahfuj, SarowerPatabandi, P. P. S. K.Bossier, PeterNorouzitallab, Parisa...
6页
查看更多>>摘要：Vibriosis caused by Vibrio campbellii and related species is amongst the major hindrance to the sustainable expansion of giant freshwater prawn Macrobrachium rosenbergii larviculture. Induction of heat shock protein Hsp70 is a natural response of stressed organisms that protect against many insults including vibriosis in aquaculture animals. Therefore, there is a great interest in searching for natural compounds that could induce Hsp70 in animals in a non-invasive manner. Previously, in a series of in vivo studies, we have shown that the phenolic compound phloroglucinol could induce Hsp70 in aquaculture organisms Macrobrachium and Artemia. This led to a significant increase in the resistance of the animals towards subsequent challenges with V. parahemolyticus. As V. parahaemolyticus belongs to the Harveyi clade similar to V. campbellii, our above findings triggered the hypothesis that phloroglucinol is a potential anti-microbial agent that could protect the freshwater prawn against V. campbellii infection. The results presented here provide evidence that the Hsp70-inducing compound phloroglucinol could induce both metaphylactic and prophylactic effects against infection stress mediated by V. campbellii. The wide-spectrum property of the compound to both prevent the occurrence and reduce the spread of V. campbellii infection in prawn larvae without affecting the larval growth makes it a potential natural agent for health management and V. campbellii-mediated disease control in freshwater prawn larvae. Overall results add new information about the functional properties of phloroglucinol and advance our knowledge of this compound as a potential antimicrobial agent for the sustainable production of giant freshwater prawns.
查看更多>>摘要：Granzyme B (GzmB) is primarily expressed by mammalian cytotoxic T cells and serves as one of the key components in the defense against viral infection by the induction of apoptosis in virus infected cells. By direct cell to cell contact and delivery into target cells by perforin, cytotoxic T cells activate apoptosis through the action of GzmB by both caspase-dependent and -independent pathways. In search for early ancestors of GzmB we have in the current study identified and characterized a GzmB homologue from a reptile, the Chinese alligator. This enzyme is encoded from the same locus as the mammalian counterparts, the chymase locus. Phage display analysis of the cleavage specificity of the recombinant alligator enzyme (named MCP1A-like) shows that it is a relatively strict Glu-ase, with strong preference for glutamic acid in the P1 position of a substrate. The majority of mammalian GzmB:s are, in marked contrast to the alligator enzyme, relatively strict Asp-ases. The alligator enzyme also showed strong preference for Ala, Pro and Gly in the P2 position and Val in the P3 position indicating that it has a narrow specificity, similar to the mammalian counterparts. Analysis of the three amino acids forming the substrate binding pocket (S1 pocket) in three amphibian homologues to MCP1A-like, from the frogs Xenopus laevis and Xenopus tropicalis, shows that these amphibian enzymes have similar substrate binding pocket as their mammalian counterparts. This finding, together with the apparent lack of GzmB homologs in fish, indicates that the ancestor of GzmB did appear with the amphibians at the base of tetrapod evolution. This study is a first step in a larger effort to understand the evolutionary processes involved in shaping anti-viral immunity in non-mammalian vertebrates.
查看更多>>摘要：Haemophilus parasuis is a widespread bacterial pathogen causing acute systemic inflammation and leading to the sudden death of piglets. Resistin, a multifunctional peptide hormone previously demonstrated to influence the inflammation in porcine, was extremely increased in H. parasuis-infected tissues. However, the mechanism of resistin expression regulation in porcine, especially during pathogen infection, remains unclear. In the present study, we explored for the first time the transcription factor and signaling pathway mediating the expression of pig resistin during H. parasuis stimulation. We found that H. parasuis induced the expression of pig resistin in a time-and dose-dependent manner via the transcription factor Ets2 in porcine alveolar macrophages during H. parasuis stimulation. Moreover, the expression of Ets2 was mediated by the activation of the p38 MAPK pathway induced by H. parasuis, thus promoting resistin production. These results revealed a novel view of the molecular mechanism of pig resistin production during acute inflammation induced by pathogenic bacteria.
查看更多>>摘要：The BTLA and HVEM are two well-characterized immune checkpoint inhibitors in humans and other mammalian species. However, the occurrence and functionality of these two molecules in non-mammalian species remain poorly understood. In the present study, we identified the BTLA and HVEM homologs from large yellow croaker (Larimichthys crocea), an economically important marine species of the perciform fish family. The Larimichthys crocea BTLA and HVEM (LcBTLA and LcHVEM) share conserved structural features to their mammalian counterparts, and they were expressed in various tissues and cells examined at different transcriptional levels, with particular abundance in immune-relevant tissues and splenic leukocytes. Immunofluorescence staining and flow cytometry analysis showed that LcHVEM and LcBTLA proteins were distributed on MHC-II+ APCs and CD4-2+ T cells, and a strong interaction between LcBTLA and LcHVEM was detected in splenic leukocytes in the mixed lymphocyte reaction (MLR). By blockade assays using anti-LcBTLA and anti-LcHVEM Abs as well as recombinant soluble LcBTLA and LcHVEM proteins in different combinations, it was found that LcBTLA-LcHVEM interactions play an important inhibitory role in the activation of alloreactive T cells using MLR as a model, and APC-initiated antigen-specific CD4-2+ T cells in response to A. hydrophila (A. h) stimulation. These observations highlight the extensive functional roles of LcBTLA and LcHVEM immune-checkpoint inhibitors in allogeneic T cell reactions, and CD4-2+ T cell-mediated adaptive immune responses in Larimichthys crocea. Thus, the BTLA-HVEM checkpoint may represent an ancient coinhibitory pathway, which was originated in fish and was conserved from fish to mammals throughout the vertebrate evolution.
Le Page, LaurenBaldwin, Cynthia L.Telfer, Janice C.
18页
查看更多>>摘要：Vaccination is the most effective medical strategy for disease prevention but there is a need to improve livestock vaccine efficacy. Understanding the structure of the immune system of swine, which are considered a gamma delta T cell "high" species, and thus, particularly how to engage their gamma delta T cells for immune responses, may allow for development of vaccine optimization strategies. The propensity of gamma delta T cells to home to specific tissues, secrete pro-inflammatory and regulatory cytokines, exhibit memory or recall responses and even function as antigen presenting cells for alpha beta T cells supports the concept that they have enormous potential for priming by next generation vaccine constructs to contribute to protective immunity. gamma delta T cells exhibit several innate-like antigen recognition properties including the ability to recognize antigen in the absence of presentation via major histocompatibility complex (MHC) molecules enabling gamma delta T cells to recognize an array of peptides but also non peptide antigens in a T cell receptor-dependent manner. gamma delta T cell subpopulations in ruminants and swine can be distinguished based on differential expression of the hybrid co-receptor and pattern recognition receptors (PRR) known as workshop cluster 1 (WC1). Expression of various PRR and other innate-like immune receptors diversifies the antigen recognition potential of gamma delta T cells. Finally, gamma delta T cells in livestock are potent producers of critical master regulator cytokines such as interferon (IFN)-gamma and interleukin (IL)-17, whose production orchestrates downstream cytokine and chemokine production by other cells, thereby shaping the immune response as a whole. Our knowledge of the biology, receptor expression and response to infectious diseases by swine gamma delta T cells is reviewed here.
查看更多>>摘要：In invertebrates, innate immune responses are the only defense against invading pathogens. The immune deficiency (IMD) signaling pathway protects invertebrates from bacterial infection by secreting antimicrobial peptides (AMPs). Fas-associated protein with death domain (FADD) activates AMPs and triggers apoptosis. However, FADD's function in crustaceans is unclear. Herein, the full-length FADD cDNA (EsFADD) was cloned from the Chinese mitten crab, Eriocheir sinensis. Vibrio parahaemolyticus infection upregulated EsFADD expression markedly. Knockdown of EsFADD in hemocytes suppressed the cytoplasm-to-nucleus translocation of transcription factor Relish under V. parahaemolyticus stimulation, which in turn reduced the expression of several AMPs. In vivo, silencing of EsFADD rendered crabs susceptible to bacterial infection and impaired their bacterial clearance. The results suggest that EsFADD is indispensable in IMD signal transduction in E. sinensis. In contrast to Drosophila, EsFADD barely promoted apoptosis. Our findings revealed the evolutionary conservation of FADD in crustaceans and provided insights into IMD signaling in invertebrates.
查看更多>>摘要：MDM2 (mouse double-minute) and p53 form a negative feedback loop and play a prominent role in preventing the induction of uncontrolled apoptosis. To better understand their potential roles in oyster Crassostrea hongkongensis, MDM2 and p53 homologs were first isolated and cloned in C. hongkongensis (named ChMDM2 and Chp53), and their mRNA expression patterns in tissues and developmental stages were analyzed. Multiple sequence alignment analysis and phylogenetic analysis of ChMDM2 and Chp53 displayed a high degree of homology and conservation. In addition, exposure to Vibrio coralliilyticus resulted in DNA damage and apoptosis in the hemocytes of C. hongkongensis, and found that the mRNA expression level of ChMDM2 was decreased, while the relative expression of Chp53 was significantly increased in the hemocytes and gills. Furthermore, fluorescence from ChMDM2-EGFP and Chp53-Red were found to be distributed in the nucleus of HEK293T cells. Besides, dual-luciferase reporter assays showed that ChMDM2 antagonized with Chp53 and participates in p53 signaling pathway. In addition, the interaction between ChMDM2 and Chp53 was confirmed strongly by Coimmunoprecipitation assays. Furthermore, the results of RNAi showed that ChMDM2 and Chp53 participated in apoptosis which induced infection of V. coralliilyticus. Taken together, our results characterized the features of ChMDM2 and Chp53, which played a critical role in apoptosis of C. hongkongensis.
NSTL
Elsevier