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• W4289837534 abstract "Macrophage surface receptors are critical for pathogen defense, as they are the gatekeepers for pathogen entry and sensing, which trigger robust immune responses. TREM2 (triggering receptor expressed on myeloid cells 2) is a transmembrane surface receptor that mediates anti-inflammatory immune signaling. A recent study showed that TREM2 is a receptor for mycolic acids in the mycobacterial cell wall and inhibits macrophage activation. However, the underlying functional mechanism of how TREM2 regulates the macrophage antimycobacterial response remains unclear. Here, we show that Mycobacterium tuberculosis, the causative agent for tuberculosis, specifically binds to human TREM2 to disable the macrophage antibacterial response. Live but not killed mycobacteria specifically trigger the upregulation of TREM2 during macrophage infection through a mechanism dependent on STING (the stimulator of interferon genes). TREM2 facilitated uptake of M. tuberculosis into macrophages and is responsible for blocking the production of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and reactive oxygen species (ROS), while enhancing the production of interferon-β (IFN-β) and IL-10. TREM2-mediated blockade of ROS production promoted the survival of M. tuberculosis within infected macrophages. Consistent with this, genetic deletion or antibody-mediated neutralization of TREM2 reduced the intracellular survival of M. tuberculosis through enhanced production of ROS. Importantly, inhibition of type I IFN signaling in TREM2-overexpressing macrophages restored the ability of these cells to produce inflammatory cytokines and ROS, resulting in normal levels of intracellular bacteria killing. Collectively, our study identifies TREM2 as an attractive host receptor for host-directed antimycobacterial therapeutics. IMPORTANCE Mycobacterium tuberculosis is one of the most ancient bacterial pathogens and remains the leading cause of death from a single bacterial agent. The success of M. tuberculosis relies greatly on its ability to parasitize and disable its host macrophages. Previous studies have found that M. tuberculosis uses its unique cell wall lipids to manipulate the immune response by binding to specific surface receptors on macrophages. Our study reveals that M. tuberculosis binds to TREM2, an immunomodulatory receptor expressed on macrophages, to facilitate a silent mode of entry. Increased levels of TREM2 triggered by intracellular sensing of M. tuberculosis promoted the intracellular survival of M. tuberculosis through type I IFN-driven inhibition of reactive oxygen species (ROS) and proinflammatory cytokine production. Importantly, deletion of TREM2 reversed the effects of silent entry and resulted in increased production of inflammatory cytokines, generation of ROS, and cell death. As such, antibody-mediated or pharmacological targeting of TREM2 could be a promising strategy for novel treatments against M. tuberculosis infection." @default.
• W4289837534 created "2022-08-05" @default.
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• W4289837534 date "2022-08-30" @default.
• W4289837534 modified "2023-10-02" @default.
• W4289837534 title "TREM2 Promotes Immune Evasion by Mycobacterium tuberculosis in Human Macrophages" @default.
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• W4289837534 cites W1667606852 @default.
• W4289837534 cites W1901576288 @default.
• W4289837534 cites W1974088684 @default.
• W4289837534 cites W1975640258 @default.
• W4289837534 cites W1977138279 @default.
• W4289837534 cites W1978554459 @default.
• W4289837534 cites W1985779248 @default.
• W4289837534 cites W1986899130 @default.
• W4289837534 cites W2001848039 @default.
• W4289837534 cites W2011041653 @default.
• W4289837534 cites W2017216199 @default.
• W4289837534 cites W2017367722 @default.
• W4289837534 cites W2022603305 @default.
• W4289837534 cites W2025056717 @default.
• W4289837534 cites W2027562913 @default.
• W4289837534 cites W2042310005 @default.
• W4289837534 cites W2051731334 @default.
• W4289837534 cites W2052395914 @default.
• W4289837534 cites W2058478749 @default.
• W4289837534 cites W2065217848 @default.
• W4289837534 cites W2071108818 @default.
• W4289837534 cites W2079958878 @default.
• W4289837534 cites W2083674522 @default.
• W4289837534 cites W2083799755 @default.
• W4289837534 cites W2084914723 @default.
• W4289837534 cites W2086964969 @default.
• W4289837534 cites W2090134990 @default.
• W4289837534 cites W2101372125 @default.
• W4289837534 cites W2102603631 @default.
• W4289837534 cites W2103333200 @default.
• W4289837534 cites W2107277218 @default.
• W4289837534 cites W2116226263 @default.
• W4289837534 cites W2116654815 @default.
• W4289837534 cites W2118751252 @default.
• W4289837534 cites W2120747728 @default.
• W4289837534 cites W2123888778 @default.
• W4289837534 cites W2124660605 @default.
• W4289837534 cites W2129442719 @default.
• W4289837534 cites W2132161879 @default.
• W4289837534 cites W2135587439 @default.
• W4289837534 cites W2160517489 @default.
• W4289837534 cites W2167017590 @default.
• W4289837534 cites W2168420558 @default.
• W4289837534 cites W2169553739 @default.
• W4289837534 cites W2170107264 @default.
• W4289837534 cites W2170841408 @default.
• W4289837534 cites W2192080449 @default.
• W4289837534 cites W2253120262 @default.
• W4289837534 cites W2326410252 @default.
• W4289837534 cites W2328938957 @default.
• W4289837534 cites W2339534121 @default.
• W4289837534 cites W2402240200 @default.
• W4289837534 cites W2418688677 @default.
• W4289837534 cites W2545393754 @default.
• W4289837534 cites W2574829263 @default.
• W4289837534 cites W2586234770 @default.
• W4289837534 cites W274725678 @default.
• W4289837534 cites W2762259514 @default.
• W4289837534 cites W2795155279 @default.
• W4289837534 cites W2884466758 @default.
• W4289837534 cites W2896695296 @default.
• W4289837534 cites W2905219483 @default.
• W4289837534 cites W2955940476 @default.
• W4289837534 cites W2965284805 @default.
• W4289837534 cites W2976082074 @default.
• W4289837534 cites W2979963278 @default.
• W4289837534 cites W3022647289 @default.
• W4289837534 cites W3024915888 @default.
• W4289837534 cites W3037497912 @default.
• W4289837534 cites W3088475679 @default.
• W4289837534 cites W3091129072 @default.
• W4289837534 cites W3122876563 @default.
• W4289837534 cites W3128527002 @default.
• W4289837534 cites W3155606790 @default.
• W4289837534 cites W3156612949 @default.
• W4289837534 cites W3165160504 @default.
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• W4289837534 doi "https://doi.org/10.1128/mbio.01456-22" @default.
• W4289837534 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35924849" @default.
• W4289837534 hasPublicationYear "2022" @default.
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