scholarly journals Leukocyte Immunoglobulin-Like Receptors A2 and A6 are Expressed in Avian Macrophages and Modulate Cytokine Production by Activating Multiple Signaling Pathways

2018 ◽  
Vol 19 (9) ◽  
pp. 2710 ◽  
Author(s):  
Anh Truong ◽  
Deivendran Rengaraj ◽  
Yeojin Hong ◽  
Ha Tran ◽  
Hoang Dang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Antigen Processing ◽  
Functional Characterization ◽  
Adaptive Immune System ◽  
Mapk Signaling ◽  
Immune Functions ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Mammalian Proteins ◽  
Close Relationship

The activating leukocyte immunoglobulin-like receptors (LILRAs) play an important role in innate immunity. However, most of the LILRA members have not been characterized in avian species including chickens. The present study is the first attempt at cloning, structural analysis and functional characterization of two LILRAs (LILRA2 and LILRA6) in chickens. Multiple sequence alignments and construction of a phylogenetic tree of chicken LILRA2 and LILRA6 with mammalian proteins revealed high conservation between chicken LILRA2 and LILRA6 and a close relationship between the chicken and mammalian proteins. The mRNA expression of LILRA2 and LILRA6 was high in chicken HD11 macrophages and the small intestine compared to that in several other tissues and cells tested. To examine the function of LILRA2 and LILRA6 in chicken immunity, LILRA2 and LILRA6 were transfected into HD11 cells. Our findings indicated that LILRA2 and LILRA6 are associated with the phosphorylation of Src kinases and SHP2, which play a regulatory role in immune functions. Moreover, LILRA6 associated with and activated MHC class I, β2-microglobulin and induced the expression of transporters associated with antigen processing but LILRA2 did not. Furthermore, both LILRA2 and LILRA6 activated JAK-STAT, NF-κB, PI3K/AKT and ERK1/2 MAPK signaling pathways and induced Th1-, Th2- and Th17-type cytokines and Toll-like receptors. Collectively, this study indicates that LILRA2 and LILRA6 are essential for macrophage-mediated immune responses and they have the potential to complement the innate and adaptive immune system against pathogens.

scholarly journals Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

2016 ◽  
Vol 113 (34) ◽  
pp. E5014-E5023 ◽  
Author(s):  
Sean C. McConnell ◽  
Kyle M. Hernandez ◽  
Dustin J. Wcisel ◽  
Ross N. Kettleborough ◽  
Derek L. Stemple ◽  
...  
Keyword(s):  
Antigen Processing ◽  
Gene Diversity ◽  
Adaptive Immune System ◽  
Immune Functions ◽  
Genomic Context ◽  
Peptide Specificity ◽  
Early Diversification ◽  
Proteasome Subunits ◽  
Divergent Haplotype ◽  
Antigen Processing And Presentation

Antigen processing and presentation genes found within the MHC are among the most highly polymorphic genes of vertebrate genomes, providing populations with diverse immune responses to a wide array of pathogens. Here, we describe transcriptome, exome, and whole-genome sequencing of clonal zebrafish, uncovering the most extensive diversity within the antigen processing and presentation genes of any species yet examined. Our CG2 clonal zebrafish assembly provides genomic context within a remarkably divergent haplotype of the core MHC region on chromosome 19 for six expressed genes not found in the zebrafish reference genome: mhc1uga, proteasome-β 9b (psmb9b), psmb8f, and previously unknown genes psmb13b, tap2d, and tap2e. We identify ancient lineages for Psmb13 within a proteasome branch previously thought to be monomorphic and provide evidence of substantial lineage diversity within each of three major trifurcations of catalytic-type proteasome subunits in vertebrates: Psmb5/Psmb8/Psmb11, Psmb6/Psmb9/Psmb12, and Psmb7/Psmb10/Psmb13. Strikingly, nearby tap2 and MHC class I genes also retain ancient sequence lineages, indicating that alternative lineages may have been preserved throughout the entire MHC pathway since early diversification of the adaptive immune system ∼500 Mya. Furthermore, polymorphisms within the three MHC pathway steps (antigen cleavage, transport, and presentation) are each predicted to alter peptide specificity. Lastly, comparative analysis shows that antigen processing gene diversity is far more extensive than previously realized (with ancient coelacanth psmb8 lineages, shark psmb13, and tap2t and psmb10 outside the teleost MHC), implying distinct immune functions and conserved roles in shaping MHC pathway evolution throughout vertebrates.

scholarly journals Functional Characterization of a Venom Protein Calreticulin in the Ectoparasitoid Pachycrepoideus vindemiae

Insects ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 29 ◽  
Author(s):  
Lei Yang ◽  
Beibei Wang ◽  
Liming Qiu ◽  
Bin Wan ◽  
Yi Yang ◽  
...  
Keyword(s):  
Expression System ◽  
Functional Characterization ◽  
Venom Gland ◽  
Amino Acid Identity ◽  
Immunohistochemical Localization ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Venom Protein ◽  
Pupal Parasitoids ◽  
Venom Proteins

Venom proteins act in the immunological interactions between parasitoids and their host insects. The effect of venom proteins on host immunity is not fully understood in pupal parasitoids. We identified the functions of a venom protein, calreticulin (PvCRT), in the pupal ectoparasitoid Pachycrepoideus vindemiae. Here, we report that PvCRT features a signal peptide and two conserved “calreticulin” domains. Multiple sequence alignments show that PvCRT shares 83.54% amino acid identity with CRT from both Pteromalus puparum and Nasonia vitripennis, which infers a close relationship among these three species. Using qPCR analysis, we found a lower expression level of PvCRT (0.27-fold) in the venom apparatus compared to the corresponding carcass. Immunohistochemical localization revealed that PvCRT was ubiquitously expressed in venom gland. The expression of the PvCRT gene in Drosophila transgenic lines via the UAS/Gal4 binary expression system reduced the self-encapsulation phenotype of tu(1)Sz1 mutants. Additionally, studies on humoral immunity indicate that PvCRT does not affect the antimicrobial immune responses of the host. This work on an ectoparasitoid will increase our understanding of venom–mediated host-parasitoid interactions.

Genome-wide identification and analysis of the eQTL lncRNAs in multiple sclerosis based on RNA-seq data

2019 ◽  
Vol 21 (3) ◽  
pp. 1023-1037 ◽  
Author(s):  
Zhijie Han ◽  
Weiwei Xue ◽  
Lin Tao ◽  
Yan Lou ◽  
Yunqing Qiu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Secondary Structure ◽  
Antigen Processing ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Mapk Signaling ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Rna Seq ◽  
Lncrna Expression

Abstract The pathogenesis of multiple sclerosis (MS) is significantly regulated by long noncoding RNAs (lncRNAs), the expression of which is substantially influenced by a number of MS-associated risk single nucleotide polymorphisms (SNPs). It is thus hypothesized that the dysregulation of lncRNA induced by genomic variants may be one of the key molecular mechanisms for the pathology of MS. However, due to the lack of sufficient data on lncRNA expression and SNP genotypes of the same MS patients, such molecular mechanisms underlying the pathology of MS remain elusive. In this study, a bioinformatics strategy was applied to obtain lncRNA expression and SNP genotype data simultaneously from 142 samples (51 MS patients and 91 controls) based on RNA-seq data, and an expression quantitative trait loci (eQTL) analysis was conducted. In total, 2383 differentially expressed lncRNAs were identified as specifically expressing in brain-related tissues, and 517 of them were affected by SNPs. Then, the functional characterization, secondary structure changes and tissue and disease specificity of the cis-eQTL SNPs and lncRNA were assessed. The cis-eQTL SNPs were substantially and specifically enriched in neurological disease and intergenic region, and the secondary structure was altered in 17.6% of all lncRNAs in MS. Finally, the weighted gene coexpression network and gene set enrichment analyses were used to investigate how the influence of SNPs on lncRNAs contributed to the pathogenesis of MS. As a result, the regulation of lncRNAs by SNPs was found to mainly influence the antigen processing/presentation and mitogen-activated protein kinases (MAPK) signaling pathway in MS. These results revealed the effectiveness of the strategy proposed in this study and give insight into the mechanism (SNP-mediated modulation of lncRNAs) underlying the pathology of MS.

scholarly journals Positive natural selection in primate genes of the type I interferon response

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Elena N. Judd ◽  
Alison R. Gilchrist ◽  
Nicholas R. Meyerson ◽  
Sara L. Sawyer
Keyword(s):  
Natural Selection ◽  
Positive Selection ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Multiple Sequence Alignments ◽  
Interferon Stimulated Genes ◽  
Interferon Induction

Abstract Background The Type I interferon response is an important first-line defense against viruses. In turn, viruses antagonize (i.e., degrade, mis-localize, etc.) many proteins in interferon pathways. Thus, hosts and viruses are locked in an evolutionary arms race for dominance of the Type I interferon pathway. As a result, many genes in interferon pathways have experienced positive natural selection in favor of new allelic forms that can better recognize viruses or escape viral antagonists. Here, we performed a holistic analysis of selective pressures acting on genes in the Type I interferon family. We initially hypothesized that the genes responsible for inducing the production of interferon would be antagonized more heavily by viruses than genes that are turned on as a result of interferon. Our logic was that viruses would have greater effect if they worked upstream of the production of interferon molecules because, once interferon is produced, hundreds of interferon-stimulated proteins would activate and the virus would need to counteract them one-by-one. Results We curated multiple sequence alignments of primate orthologs for 131 genes active in interferon production and signaling (herein, “induction” genes), 100 interferon-stimulated genes, and 100 randomly chosen genes. We analyzed each multiple sequence alignment for the signatures of recurrent positive selection. Counter to our hypothesis, we found the interferon-stimulated genes, and not interferon induction genes, are evolving significantly more rapidly than a random set of genes. Interferon induction genes evolve in a way that is indistinguishable from a matched set of random genes (22% and 18% of genes bear signatures of positive selection, respectively). In contrast, interferon-stimulated genes evolve differently, with 33% of genes evolving under positive selection and containing a significantly higher fraction of codons that have experienced selection for recurrent replacement of the encoded amino acid. Conclusion Viruses may antagonize individual products of the interferon response more often than trying to neutralize the system altogether.

scholarly journals Respiratory syncytial virus B sequence analysis reveals a novel early genotype

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Juan C. Muñoz-Escalante ◽  
Andreu Comas-García ◽  
Sofía Bernal-Silva ◽  
Daniel E. Noyola
Keyword(s):  
Molecular Markers ◽  
Respiratory Syncytial Virus ◽  
Maximum Likelihood ◽  
Respiratory Infections ◽  
Phylogenetic Analyses ◽  
Detection Methods ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Individual Gene ◽  
Syncytial Virus

AbstractRespiratory syncytial virus (RSV) is a major cause of respiratory infections and is classified in two main groups, RSV-A and RSV-B, with multiple genotypes within each of them. For RSV-B, more than 30 genotypes have been described, without consensus on their definition. The lack of genotype assignation criteria has a direct impact on viral evolution understanding, development of viral detection methods as well as vaccines design. Here we analyzed the totality of complete RSV-B G gene ectodomain sequences published in GenBank until September 2018 (n = 2190) including 478 complete genome sequences using maximum likelihood and Bayesian phylogenetic analyses, as well as intergenotypic and intragenotypic distance matrices, in order to generate a systematic genotype assignation. Individual RSV-B genes were also assessed using maximum likelihood phylogenetic analyses and multiple sequence alignments were used to identify molecular markers associated to specific genotypes. Analyses of the complete G gene ectodomain region, sequences clustering patterns, and the presence of molecular markers of each individual gene indicate that the 37 previously described genotypes can be classified into fifteen distinct genotypes: BA, BA-C, BA-CC, CB1-THB, GB1-GB4, GB6, JAB1-NZB2, SAB1, SAB2, SAB4, URU2 and a novel early circulating genotype characterized in the present study and designated GB0.

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