biostudies-literatureUnknown12Bomfim CCBFundação de Amparo à Pesquisa do Estado de São PauloDivision of Cancer Prevention, National Cancer InstituteDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesIrg1 is an enzyme that generates itaconate, a metabolite that plays a key role in the regulation of inflammatory responses. Previous studies have implicated Irg1 as an important mediator in preventing excessive inflammation and tissue damage in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection. Here, we investigated the pattern recognition receptors and signaling pathways by which <i>Mtb</i> triggers Irg1 gene expression by comparing the responses of control and genetically deficient BMDMs. Using this approach, we demonstrated partial roles for TLR-2 (but not TLR-4 or -9), MyD88 and NFκB signaling in Irg1 induction by <i>Mtb</i> bacilli. In addition, drug inhibition studies revealed major requirements for phagocytosis and endosomal acidification in Irg1 expression triggered by <i>MtFrontiers in cellular and infection microbiology862582https://www.ebi.ac.uk/biostudies/studies/S-EPMC9109611biostudies-literature<i>Mycobacterium tuberculosis</i> Induces <i>Irg1</i> in Murine Macrophages by a Pathway Involving Both TLR-2 and STING/IFNAR Signaling and Requiring Bacterial Phagocytosis.PMC9109611Chari RSher ACorrea AASD'Imperio Lima MRMittereder LAmaral EPMcVicar DWNamasivayam SFisher LWeiss JMCosta DLSwamydas MMoayeri MMcCann KBomfim CCBfalse<i>Mycobacterium tuberculosis</i> Induces <i>Irg1</i> in Murine Macrophages by a Pathway Involving Both TLR-2 and STING/IFNAR Signaling and Requiring Bacterial Phagocytosis.Irg1 is an enzyme that generates itaconate, a metabolite that plays a key role in the regulation of inflammatory responses. Previous studies have implicated Irg1 as an important mediator in preventing excessive inflammation and tissue damage in <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection. Here, we investigated the pattern recognition receptors and signaling pathways by which <i>Mtb</i> triggers Irg1 gene expression by comparing the responses of control and genetically deficient BMDMs. Using this approach, we demonstrated partial roles for TLR-2 (but not TLR-4 or -9), MyD88 and NFκB signaling in Irg1 induction by <i>Mtb</i> bacilli. In addition, drug inhibition studies revealed major requirements for phagocytosis and endosomal acidification in Irg1 expression triggered by <i>Mt2022-01-01T00:00:00Z20222026-04-08T09:31:21.316Z2024-12-03T23:30:58.229ZS-EPMC91096113558624910.3389/fcimb.2022.862582