scholarly journals Faculty Opinions recommendation of Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence.

2017 ◽  
Author(s):  
Susanne Muehlich ◽  
Constanze Mittermeier
Keyword(s):  
Innate Immune ◽  
Immune Sensing ◽  
Innate Immune Sensing

scholarly journals Special Issue: “Innate Immune Sensing of Viruses and Viral Evasion”

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 567
Author(s):  
Renate König ◽  
Carsten Münk
Keyword(s):  
Innate Immunity ◽  
Innate Immune ◽  
Special Issue ◽  
First Line ◽  
Review Articles ◽  
Immune Sensing ◽  
Innate Immune Sensing ◽  
Viral Evasion

In this Special Issue, a wide variety of original and review articles provide a timely overview of how viruses are recognized by and evade from cellular innate immunity, which represents the first line of defense against viruses [...]

scholarly journals The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype

2018 ◽  
Author(s):  
Priya Hari ◽  
Fraser R. Millar ◽  
Nuria Tarrats ◽  
Jodie Birch ◽  
Curtis J. Rink ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Innate Immune ◽  
Toll Like Receptor ◽  
Cycle Arrest ◽  
Secretory Phenotype ◽  
Immune Sensing ◽  
Molecular Patterns ◽  
Innate Immune Sensing

ABSTRACTCellular senescence is a stress response program characterised by a robust cell cycle arrest and the induction of a pro-inflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that during oncogene-induced senescence (OIS), the Toll-like receptor TLR2 and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumour suppressors p53-p21CIP1, p16INK4a and p15INK4b, and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAA) that, in turn, function as the damage associated molecular patterns (DAMPs) signalling through TLR2 in OIS. Finally, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAA expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.

scholarly journals Bloom syndrome protein restrains innate immune sensing of micronuclei by cGAS

2019 ◽  
Vol 216 (5) ◽  
pp. 1199-1213 ◽  
Author(s):  
Matthieu Gratia ◽  
Mathieu P. Rodero ◽  
Cécile Conrad ◽  
Elias Bou Samra ◽  
Mathieu Maurin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Immune Responses ◽  
Genome Instability ◽  
Bloom Syndrome ◽  
Innate Immune ◽  
Genome Integrity ◽  
Immune Sensing ◽  
Syndrome Protein ◽  
Innate Immune Sensing ◽  
Exonuclease Trex1

Cellular innate immune sensors of DNA are essential for host defense against invading pathogens. However, the presence of self-DNA inside cells poses a risk of triggering unchecked immune responses. The mechanisms limiting induction of inflammation by self-DNA are poorly understood. BLM RecQ–like helicase is essential for genome integrity and is deficient in Bloom syndrome (BS), a rare genetic disease characterized by genome instability, accumulation of micronuclei, susceptibility to cancer, and immunodeficiency. Here, we show that BLM-deficient fibroblasts show constitutive up-regulation of inflammatory interferon-stimulated gene (ISG) expression, which is mediated by the cGAS–STING–IRF3 cytosolic DNA–sensing pathway. Increased DNA damage or down-regulation of the cytoplasmic exonuclease TREX1 enhances ISG expression in BLM-deficient fibroblasts. cGAS-containing cytoplasmic micronuclei are increased in BS cells. Finally, BS patients demonstrate elevated ISG expression in peripheral blood. These results reveal that BLM limits ISG induction, thus connecting DNA damage to cellular innate immune response, which may contribute to human pathogenesis.

scholarly journals BK Polyomavirus Evades Innate Immune Sensing by Disrupting the Mitochondrial Network and Promotes Mitophagy

iScience ◽  
2020 ◽  
Vol 23 (7) ◽  
pp. 101257 ◽  
Author(s):  
Julia Manzetti ◽  
Fabian H. Weissbach ◽  
Fabrice E. Graf ◽  
Gunhild Unterstab ◽  
Marion Wernli ◽  
...  
Keyword(s):  
Innate Immune ◽  
Mitochondrial Network ◽  
Bk Polyomavirus ◽  
Immune Sensing ◽  
Innate Immune Sensing

scholarly journals Microbiota regulates type 1 diabetes through Toll-like receptors

2015 ◽  
Vol 112 (32) ◽  
pp. 9973-9977 ◽  
Author(s):  
Michael P. Burrows ◽  
Pavel Volchkov ◽  
Koichi S. Kobayashi ◽  
Alexander V. Chervonsky
Keyword(s):  
Type 1 Diabetes ◽  
Nod Mice ◽  
Intestinal Bacteria ◽  
Primary Response ◽  
Innate Immune ◽  
Specific Pathogen ◽  
Immune Sensing ◽  
Critical Components ◽  
Innate Immune Sensing

Deletion of the innate immune adaptor myeloid differentiation primary response gene 88 (MyD88) in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) results in microbiota-dependent protection from the disease: MyD88-negative mice in germ-free (GF), but not in specific pathogen-free conditions develop the disease. These results could be explained by expansion of particular protective bacteria (“specific lineage hypothesis”) or by dominance of negative (tolerizing) signaling over proinflammatory signaling (“balanced signal hypothesis”) in mutant mice. Here we found that colonization of GF mice with a variety of intestinal bacteria was capable of reducing T1D in MyD88-negative (but not wild-type NOD mice), favoring the balanced signal hypothesis. However, the receptors and signaling pathways involved in prevention or facilitation of the disease remained unknown. The protective signals triggered by the microbiota were revealed by testing NOD mice lacking MyD88 in combination with knockouts of several critical components of innate immune sensing for development of T1D. Only MyD88- and TIR-domain containing adapter inducing IFN β (TRIF) double deficient NOD mice developed the disease. Thus, TRIF signaling (likely downstream of Toll-like receptor 4, TLR4) serves as one of the microbiota-induced tolerizing pathways. At the same time another TLR (TLR2) provided prodiabetic signaling by controlling the microbiota, as reduction in T1D incidence caused by TLR2 deletion was reversed in GF TLR2-negative mice. Our results support the balanced signal hypothesis, in which microbes provide signals that both promote and inhibit autoimmunity by signaling through different receptors, including receptors of the TLR family.

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