TMEM173 Drives Lethal Coagulation in Sepsis.

Cell Host & Microbe
Hui ZhangDaolin Tang

Abstract

The discovery of TMEM173/STING-dependent innate immunity has recently provided guidance for the prevention and management of inflammatory disorders. Here, we show that myeloid TMEM173 occupies an essential role in regulating coagulation in bacterial infections through a mechanism independent of type I interferon response. Mechanistically, TMEM173 binding to ITPR1 controls calcium release from the endoplasmic reticulum in macrophages and monocytes. The TMEM173-dependent increase in cytosolic calcium drives Gasdermin D (GSDMD) cleavage and activation, which triggers the release of F3, the key initiator of blood coagulation. Genetic or pharmacological inhibition of the TMEM173-GSDMD-F3 pathway blocks systemic coagulation and improves animal survival in three models of sepsis (cecal ligation and puncture or bacteremia with Escherichia coli or Streptococcus pneumoniae infection). The upregulation of the TMEM173 pathway correlates with the severity of disseminated intravascular coagulation and mortality in patients with sepsis. Thus, TMEM173 is a key regulator of blood clotting during lethal bacterial infections.

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Citations

May 23, 2020·PLoS Pathogens·Daolin TangRui Kang
Jun 24, 2020·Emerging Microbes & Infections·Jean-Marie BerthelotFrédéric Lioté
Aug 26, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paul B ComishDaolin Tang
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Oct 10, 2020·Clinical & Translational Immunology·Lipeng TangBoudewijn Mt Burgering
Jan 20, 2021·Cell Death and Differentiation·Xin ChenDaolin Tang
Jan 20, 2021·Signal Transduction and Targeted Therapy·Nian WangRui Kang
Jan 25, 2021·Journal of Experimental & Clinical Cancer Research : CR·Qiongyuan HuWenxian Guan
Dec 18, 2020·Frontiers in Immunology·Weinian LiaoJunping Wang
Feb 23, 2021·American Journal of Physiology. Renal Physiology·Wei GongZhanjun Jia
Feb 24, 2021·Immunopharmacology and Immunotoxicology·Zhaoxue HuHuibin Zhang
Apr 3, 2021·Frontiers in Immunology·Runliu WuRui Kang
Mar 30, 2021·Frontiers in Pharmacology·Nian WangDaolin Tang
Apr 10, 2020·Cell Host & Microbe·Jolien VandewalleClaude Libert
Apr 22, 2021·Family Medicine and Community Health·Hazem A Sayed AhmedHani Aiash
Apr 29, 2021·Trends in Immunology·Daolin TangRui Kang
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Jun 4, 2021·Signal Transduction and Targeted Therapy·Ruoxi ZhangDaolin Tang
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Aug 3, 2021·Chinese Journal of Traumatology = Zhonghua Chuang Shang Za Zhi·Ruo-Xi ZhangDao-Lin Tang
Aug 31, 2021·Clinical and Translational Medicine·Tiantian DuLutao Du

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