{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:46:26Z","timestamp":1782283586328,"version":"3.54.5"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Macrophages undergo dynamic metabolic reprogramming that critically shapes their functional polarization and antimicrobial responses during mycobacterial infection. This review integrates current knowledge on how infection reprograms major metabolic pathways in macrophages. Mycobacterial infection triggers a complex and often dual-purposed rewiring of glycolysis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism. Pathogens actively manipulate these pathways to simultaneously suppress host antimicrobial effector functions and acquire nutrients for their own survival. Enhanced glycolysis, typically linked to M1 macrophages, can be exploited by the pathogen. Reprogramming of the TCA cycle, particularly through metabolites like itaconate, drives macrophages polarization toward an M2 phenotype that favors bacterial persistence. Amino acid metabolism becomes a site of metabolic competition where the bacterium secures substrates such as arginine and tryptophan to induce M2 phenotype, while the host attempts to sustain M1 macrophage functions through glutamine metabolism and the arginine nitric oxide pathway. Fatty acid metabolism further contributes to macrophage polarization in a context dependent manner. Understanding this immunometabolic interplay provides novel insights into tuberculosis pathogenesis and highlights metabolic pathways as potential targets for host-directed therapies. Future research should clarify the heterogeneity of metabolic responses across different mycobacterial species, infection stages, and macrophage subsets to guide therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1806805","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:47:17Z","timestamp":1782280037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic reprogramming of macrophages during mycobacterial infection: a review of immunometabolic crosstalk and pathogen manipulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaohe","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Center, Shandong Second Provincial General Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingfan","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Thyroid and Breast Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongquan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Center, Shandong Second Provincial General Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Center, Shandong Second Provincial General Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.775326","article-title":"Foam cell macrophages in tuberculosis","volume":"12","author":"Agarwal","year":"2021","journal-title":"Front. 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