scholarly journals NOD2, RIP2 and IRF5 Play a Critical Role in the Type I Interferon Response to Mycobacterium tuberculosis

2009 ◽  
Vol 5 (7) ◽  
pp. e1000500 ◽  
Author(s):  
Amit K. Pandey ◽  
Yibin Yang ◽  
Zhaozhao Jiang ◽  
Sarah M. Fortune ◽  
Francois Coulombe ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Type I Interferon ◽  
Critical Role ◽  
Interferon Response ◽  
Type I

scholarly journals Critical Role of Constitutive Type I Interferon Response in Bronchial Epithelial Cell to Influenza Infection

PLoS ONE ◽  
2012 ◽  
Vol 7 (3) ◽  
pp. e32947 ◽  
Author(s):  
Alan C-Y. Hsu ◽  
Kristy Parsons ◽  
Ian Barr ◽  
Sue Lowther ◽  
Deborah Middleton ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Type I Interferon ◽  
Influenza Infection ◽  
Critical Role ◽  
Bronchial Epithelial Cell ◽  
Interferon Response ◽  
Type I ◽  
Bronchial Epithelial

A critical role of interferon-induced protein IFP35 in the type I interferon response in cells induced by foot-and-mouth disease virus (FMDV) protein 2C

2014 ◽  
Vol 159 (11) ◽  
pp. 2925-2935 ◽  
Author(s):  
Wei Zheng ◽  
Xiaying Li ◽  
Jianchang Wang ◽  
Xiaoqi Li ◽  
Hong Cao ◽  
...  
Keyword(s):  
Disease Virus ◽  
Type I Interferon ◽  
Critical Role ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Interferon Response ◽  
Type I ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Mycobacterium tuberculosis MmsA (Rv0753c) Interacts with STING and Blunts the Type I Interferon Response

mBio ◽  
2020 ◽  
Vol 11 (6) ◽  
Author(s):  
Yifan Sun ◽  
Wei Zhang ◽  
Chunsheng Dong ◽  
Sidong Xiong
Keyword(s):  
Mass Spectrometry ◽  
Mycobacterium Tuberculosis ◽  
Proteomic Analysis ◽  
Type I Interferon ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn ◽  
Content Type ◽  
C Terminus ◽  
Autophagic Degradation

ABSTRACT Type I interferon (IFN) plays an important role in Mycobacterium tuberculosis persistence and disease pathogenesis. M. tuberculosis has evolved a number of mechanisms to evade host immune surveillance. However, it is unclear how the type I IFN response is tightly regulated by the M. tuberculosis determinants. Stimulator of interferon genes (STING) is an essential adaptor for type I IFN production triggered by M. tuberculosis genomic DNA or cyclic dinucleotides upon infection. To investigate how the type I IFN response is regulated by M. tuberculosis determinants, immunoprecipitation-mass spectrometry-based (IP-MS) proteomic analysis was performed to screen proteins interacting with STING in the context of M. tuberculosis infection. Among the many predicted candidates interacting with STING, the M. tuberculosis coding protein Rv0753c (MmsA) was identified. We confirmed that MmsA binds and colocalizes with STING, and the N-terminal regions of MmsA (amino acids [aa] 1 to 251) and STING (aa 1 TO 190) are responsible for MmsA-STING interaction. Type I IFN production was impaired with exogenous expression of MmsA in RAW264.7 cells. MmsA inhibited the STING-TBK1-IRF3 pathway, as evidenced by reduced STING levelS and subsequent IRF3 activation. Furthermore, MmsA facilitated p62-mediated STING autophagic degradation by binding p62 with its C terminus (aa 252 to 455), which may account for the negative regulation of M. tuberculosis MmsA in STING-mediated type I IFN production. Additionally, the M. tuberculosis mmsA R138W mutation, detected in a hypervirulent clinical isolate, enhanced the degradation of STING, implying the important relevance of MmsA in disease outcome. Together, we report a novel mechanism where M. tuberculosis MmsA serves as an antagonist of type I IFN response by targeting STING with p62-mediated autophagic degradation. IMPORTANCE It is unclear how the type I IFN response is regulated by mycobacterial determinants. Here, we characterized the previously unreported role of M. tuberculosis MmsA in immunological regulation of type I IFN response by targeting the central adaptor STING in the DNA sensing pathway. We identified STING-interacting MmsA by coimmunoprecipitation-mass spectrometry-based (IP-MS) proteomic analysis and showed MmsA interacting with STING and autophagy receptor p62 via its N terminus and C terminus, respectively. We also showed that MmsA downregulated type I IFN by promoting p62-mediated STING degradation. Moreover, the MmsA mutant R138W is potentially associated with the virulence of M. tuberculosis clinical strains owing to the modulation of STING protein. Our results provide novel insights into the regulatory mechanism of type I IFN response manipulated by mycobacterial MmsA and the additional cross talk between autophagy and STING in M. tuberculosis infection, wherein a protein from microbial pathogens induces autophagic degradation of host innate immune molecules.

scholarly journals TRIM14 is a key regulator of the type I interferon response during Mycobacterium tuberculosis infection

2019 ◽  
Author(s):  
Caitlyn T. Hoffpauir ◽  
Samantha L. Bell ◽  
Kelsi O. West ◽  
Tao Jing ◽  
Sylvia Torres-Odio ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Nucleic Acid ◽  
Type I Interferon ◽  
Negative Regulator ◽  
Interferon Response ◽  
Cytokine Signaling ◽  
Type I ◽  
Type I Ifn ◽  
Mycobacterium Tuberculosis Infection ◽  
Innate Immune Signaling

ABSTRACTTripartite motif-containing proteins (TRIMs) play a variety of recently described roles in innate immunity. While many TRIMs regulate type I interferon (IFN) expression following cytosolic nucleic acid sensing of viruses, their contribution to innate immune signaling and gene expression during bacterial infection remains largely unknown. Because Mycobacterium tuberculosis is a potent activator of cGAS-dependent cytosolic DNA sensing, we set out to investigate a role for TRIM proteins in regulating macrophage responses to M. tuberculosis. Here we demonstrate that TRIM14, a non-canonical TRIM that lacks an E3 ligase RING domain, is a critical negative regulator of the type I IFN response in macrophages. We show that TRIM14 physically interacts with both cGAS and TBK1 and that macrophages lacking TRIM14 dramatically hyperinduce interferon stimulated gene (ISG) expression following cytosolic nucleic acid transfection, IFN-β treatment, and M. tuberculosis infection. Consistent with a defect in resolution of the type I IFN response, Trim14 knockout (KO) macrophages have more phospho-Ser754 STAT3 relative to phospho-727 and fail to upregulate the STAT3 target Socs3 (Suppressor of Cytokine Signaling 3), which is required to turn off IFNAR signaling. These data support a model whereby TRIM14 acts as a scaffold between TBK1 and STAT3 to promote phosphorylation of STAT3 at Ser727 and enhance negative regulation of ISG expression. Remarkably, Trim14 KO macrophages hyperinduce antimicrobials like Inos2 and are significantly better than control cells at limiting M. tuberculosis replication. Collectively, these data reveal a previously unappreciated role for TRIM14 in resolving type I IFN responses and controlling M. tuberculosis infection.

Viral Invasion and Type I Interferon Response Characterize the Immunophenotypes during COVID-19 Infection

2020 ◽  
Author(s):  
Lai Wei ◽  
Siqi Ming ◽  
Bin Zou ◽  
Yongjian Wu ◽  
Zhongsi Hong ◽  
...  
Keyword(s):  
Type I Interferon ◽  
Interferon Response ◽  
Type I

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 P72.06 NLRP4-Mediated Type I Interferon Response Benefits Immune Checkpoint Therapy Through Redirecting CD8+ T Cell Distribution in TME

2021 ◽  
Vol 16 (3) ◽  
pp. S567-S568
Author(s):  
L. Xia ◽  
H. Wang ◽  
H. Dong ◽  
Y. Wang ◽  
S. Lu
Keyword(s):  
T Cell ◽  
Immune Checkpoint ◽  
Type I Interferon ◽  
Cd8 T Cell ◽  
Interferon Response ◽  
Type I ◽  
Cell Distribution
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