scholarly journals The Intestinal Microbiome Restricts Alphavirus Infection and Dissemination through a Bile Acid-Type I IFN Signaling Axis

Cell ◽  
2020 ◽  
Vol 182 (4) ◽  
pp. 901-918.e18 ◽  
Author(s):  
Emma S. Winkler ◽  
Swathi Shrihari ◽  
Barry L. Hykes ◽  
Scott A. Handley ◽  
Prabhakar S. Andhey ◽  
...  
Keyword(s):  
Bile Acid ◽  
Intestinal Microbiome ◽  
Type I ◽  
Type I Ifn ◽  
Acid Type ◽  
Signaling Axis ◽  
Alphavirus Infection

scholarly journals STAT1 maintains naïve CD8 + T cell quiescence by suppressing the type I IFN-STAT4-mTORC1 signaling axis

2021 ◽  
Vol 7 (36) ◽  
Author(s):  
Yoon-Chul Kye ◽  
Gil-Woo Lee ◽  
Sung-Woo Lee ◽  
Young-Jun Ju ◽  
Hee-Ok Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Cd8 T Cell ◽  
Type I ◽  
Type I Ifn ◽  
Mtorc1 Signaling ◽  
Cell Quiescence ◽  
Signaling Axis

scholarly journals MAP4-regulated dynein-dependent trafficking of BTN3A1 controls the TBK1–IRF3 signaling axis

2016 ◽  
Vol 113 (50) ◽  
pp. 14390-14395 ◽  
Author(s):  
Minji Seo ◽  
Seong-Ok Lee ◽  
Ji-Hoon Kim ◽  
Yujin Hong ◽  
Seongchan Kim ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Upstream Regulator ◽  
Spatiotemporal Regulation ◽  
Signaling Axis ◽  
Dependent Transport ◽  
Irf3 Activation

The innate immune system detects viral nucleic acids and induces type I interferon (IFN) responses. The RNA- and DNA-sensing pathways converge on the protein kinase TANK-binding kinase 1 (TBK1) and the transcription factor IFN-regulatory factor 3 (IRF3). Activation of the IFN signaling pathway is known to trigger the redistribution of key signaling molecules to punctate perinuclear structures, but the mediators of this spatiotemporal regulation have yet to be defined. Here we identify butyrophilin 3A1 (BTN3A1) as a positive regulator of nucleic acid-mediated type I IFN signaling. Depletion of BTN3A1 inhibits the cytoplasmic nucleic acid- or virus-triggered activation of IFN-β production. In the resting state, BTN3A1 is constitutively associated with TBK1. Stimulation with nucleic acids induces the redistribution of the BTN3A1–TBK1 complex to the perinuclear region, where BTN3A1 mediates the interaction between TBK1 and IRF3, leading to the phosphorylation of IRF3. Furthermore, we show that microtubule-associated protein 4 (MAP4) controls the dynein-dependent transport of BTN3A1 in response to nucleic acid stimulation, thereby identifying MAP4 as an upstream regulator of BTN3A1. Thus, the depletion of either MAP4 or BTN3A1 impairs cytosolic DNA- or RNA-mediated type I IFN responses. Our findings demonstrate a critical role for MAP4 and BTN3A1 in the spatiotemporal regulation of TBK1, a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling.

scholarly journals Loss of Mitochondrial Protease CLPP Activates Type I IFN Responses through the Mitochondrial DNA–cGAS–STING Signaling Axis

2021 ◽  
pp. ji2001016
Author(s):  
Sylvia Torres-Odio ◽  
Yuanjiu Lei ◽  
Suzana Gispert ◽  
Antonia Maletzko ◽  
Jana Key ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Type I ◽  
Type I Ifn ◽  
Signaling Axis

scholarly journals The Intestinal Microbiome Primes Host Innate Immunity Against Enteric Virus Systemic Infection Through Type I Interferon

2021 ◽  
Author(s):  
Xiao-Lian Yang ◽  
Gan Wang ◽  
Jin-Yan Xie ◽  
Han Li ◽  
Wei Liu ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Type I Interferon ◽  
Systemic Infection ◽  
Enteric Virus ◽  
Encephalomyocarditis Virus ◽  
Commensal Bacteria ◽  
Intestinal Microbiome ◽  
Type I ◽  
Type I Ifn ◽  
Host Innate Immunity

Abstract BackgroundIntestinal microbiomes are of vital importance in antagonizing systemic viral infection. However, very little literature has shown whether commensal bacteria play a crucial role in protecting enteric virus systemic infection from the aspect of modulating host innate immunity. Also, only a few specific commensal bacteria species have been revealed to be capable in regulating antiviral innate immune responses mediated by type I interferon (IFN). The underlying mechanisms have not yet been elucidated.ResultsWe utilized an enteric virus, encephalomyocarditis virus (EMCV) to inoculate PBS-treated or antibiotic cocktail-administrated mice (Abx) orally or intraperitoneally to examine the impact of microbiota depletion on virulence and viral replication in vivo. Microbiota depletion exacerbated the mortality, neuropathogenesis, viremia and viral burden in brain following EMCV infection. Furthermore, Abx-treated mice exhibited severely diminished macrophage activation and impaired type I IFN production and ISG expression in PBMC, spleen or brain. With the help of fecal bacterial 16S rRNA sequencing of PBS and Abx mice, we identified a single commensal bacterium Blautia coccoides (B. coccoides) that can restore macrophage- and IFNAR-dependent type I IFN responses to restrict systemic enteric virus infection.ConclusionOur present study demonstrates that intestinal microbiome is fundamental for protecting from enteric virus systemic infection through activating macrophages and type I IFN responses. Reconstitution with B. coccoides can inhibit enteric virus infection and mitigate its neuropathogenesis by activating IFN-I and ISG responses in macrophages via IFNAR- and STAT1-mediated signaling pathway.

PLASMACYTOID DENDRITIC CELLS FUNCTION IN HIV INFECTION

2008 ◽  
Vol 31 (4) ◽  
pp. 13
Author(s):  
Martin Hyrcza ◽  
Mario Ostrowski ◽  
Sandy Der
Keyword(s):  
Dendritic Cells ◽  
Influenza Virus ◽  
Hiv Infection ◽  
Gene Transcription ◽  
Sendai Virus ◽  
Plasmacytoid Dendritic Cells ◽  
Type I Interferons ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifn

Plasmacytoid dendritic cells (pDCs) are innate immune cells able to produce large quantities of type I interferons (IFN) when activated. Human immunodeficiency virus (HIV)-infected patients show generalized immune dysfunction characterized in part by chronic interferon response. In this study we investigated the role of dendritic cells inactivating and maintaining this response. Specifically we compared the IFN geneactivity in pDCs in response to several viruses and TLR agonists. We hypothesized that 1) the pattern of IFN gene transcription would differ in pDCs treated with HIV than with other agents, and 2) that pDCs from patients from different stages of disease would respond differently to the stimulations. To test these hypotheses, we obtained pDCs from 15 HIV-infected and uninfected individuals and treated freshly isolated pDCs with either HIV (BAL strain), influenza virus (A/PR/8/34), Sendai virus (Cantell strain), TLR7 agonist(imiquimod), or TLR9 agonist (CpG-ODN) for 6h. Type I IFN gene transcription was monitored by real time qPCRfor IFNA1, A2, A5, A6, A8,A17, B1, and E1, and cytokine levels were assayed by Cytometric Bead Arrays forTNF?, IL6, IL8, IL10, IL1?, and IL12p70. pDC function as determined by these two assays showed no difference between HIV-infected and uninfected patients or between patients with early or chronic infection. Specifically, HIV did notinduce type I IFN gene expression, whereas influenza virus, Sendai virus and imiquimod did. Similarly, HIV failed to induce any cytokine release from pDCs in contrast to influenza virus, Sendai virus and imiquimod, which stimulatedrelease of TNF?, IL6, or IL8. Together these results suggest that the reaction of pDCs to HIV virus is quantitatively different from the response to agents such as virus, Sendai virus, and imiquimod. In addition, pDCs from HIV-infected persons have responses similar to pDCs from uninfected donors, suggesting, that the DC function may not be affected by HIV infection.

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