{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T05:05:23Z","timestamp":1780031123742,"version":"3.53.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aims to explore the association between Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) expression and tuberculosis pathogenesis, with particular focus on its potential correlation with established macrophage polarization markers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The inflammatory pathology of lung tissues in mock-infected mice was evaluated using hematoxylin and eosin (H&amp;amp;E) staining. Additionally, the expression and localization of M1\/M2 macrophage-specific markers and TREM2 were assessed via immunohistochemical (IHC) staining. The expression levels and localization of M1\/M2 macrophage-associated cytokines, including IL-10 and IL-6, were measured in peripheral blood using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (qRT-PCR).\n                      <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                      suspensions were co-cultured with THP-1-derived macrophages and RAW264.7 macrophages. Temporal changes in the expression of TREM2 and M1\/M2 macrophage-specific markers were analyzed at different time points using qRT-PCR and Western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      I In the experimental group of mice, lung lesions exhibited widened alveolar septa, interstitial edema, and extensive infiltration of inflammatory cells and erythrocytes. TREM2 and inflammatory markers (iNOS and IL-10) showed significant positive expression in the infected lung tissues. Compared to the control group, the Mycobacterium-infected mouse model displayed significantly higher mRNA expression levels of TREM2, along with increased IL-10 and IL-6 production. Following co-culture with\n                      <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                      , both THP-1-derived macrophages and RAW264.7 cells exhibited upregulated TREM2 mRNA and protein expression. This upregulation was more closely associated with M2-type macrophage markers than with M1-type markers. Preferential TREM2 expression in M2 macrophages post-infection Notably, after\n                      <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n                      infection, TREM2 expression was significantly more pronounced in M2-polarized macrophages compared to their M1 counterparts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      TREM2 expression was significantly upregulated in lung tissues of tuberculosis-infected murine models, correlating strongly with increased expression of macrophage-derived cytokines. Notably,\n                      <jats:italic>in vitro<\/jats:italic>\n                      infection studies revealed that TREM2 upregulation followed a temporal pattern parallel to M2 macrophage marker expression. These findings suggest that TREM2 may be associated with M2 macrophage polarization and could potentially contribute to this phenotypic shift, a process that may play a critical role in the immunological mechanisms underlying tuberculosis pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1835965","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:52:57Z","timestamp":1780030377000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal upregulation of TREM2 parallel to M2 macrophage marker expression in tuberculosis: implications for macrophage polarization regulation"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaoqian","family":"Shang","sequence":"first","affiliation":[{"name":"Clinical Laboratory Center, The third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Key Laboratory of High Incidence Diseases in Research in Xinjiang (Xinjiang Medical University), Ministry of Education","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naifeisha","family":"Maimaiti","sequence":"additional","affiliation":[{"name":"Department of Pathology, People's Hospital of Xinjiang Uygur Autonomous Region","place":["Urumuqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengming","family":"Tian","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, The third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Key Laboratory of High Incidence Diseases in Research in Xinjiang (Xinjiang Medical University), Ministry of Education","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunbo","family":"Liao","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, The Fifth Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hu","family":"Sun","sequence":"additional","affiliation":[{"name":"The Frist Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, The third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Key Laboratory of High Incidence Diseases in Research in Xinjiang (Xinjiang Medical University), Ministry of Education","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weina","family":"Kong","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, The third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Key Laboratory of High Incidence Diseases in Research in Xinjiang (Xinjiang Medical University), Ministry of Education","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiannan","family":"Sun","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, The third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Key Laboratory of High Incidence Diseases in Research in Xinjiang (Xinjiang Medical University), Ministry of Education","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"The Fifth Affiliated Hospital of Xinjiang Medical University","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Ma","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Center, The third Affiliated Teaching Hospital of Xinjiang Medical University (Affiliated Cancer Hospital), Key Laboratory of High Incidence Diseases in Research in Xinjiang (Xinjiang Medical University), Ministry of Education","place":["Urumqi, Xinjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B9","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1038\/35074114","article-title":"TREM-1 amplifies inflammation and is a crucial mediator of septic shock","volume":"410","author":"Bouchon","year":"2001","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","first-page":"17762","DOI":"10.1038\/s41598-017-17999-3","article-title":"Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation","volume":"7","author":"Castillo","year":"2017","journal-title":"Sci. Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nri1106","article-title":"TREMs in the immune system and beyond","volume":"3","author":"Colonna","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1053\/j.gastro.2012.10.040","article-title":"Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response","volume":"144","author":"Correale","year":"2013","journal-title":"Gastroenterology"},{"key":"B1","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1146\/annurev.micro.57.030502.091033","article-title":"The secret lives of the pathogenic mycobacteria","volume":"57","author":"Cosma","year":"2003","journal-title":"Annu. Rev. Microbiol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01456-22","article-title":"TREM2 promotes immune evasion by Mycobacterium tuberculosis in human macrophages","volume":"13","author":"Dabla","year":"2022","journal-title":"mBio"},{"key":"B4","doi-asserted-by":"publisher","first-page":"409","DOI":"10.15585\/mmwr.mm7012a1","article-title":"Tuberculosis\u2014United states, 2020","volume":"70","author":"Deutsch-Feldman","year":"2021","journal-title":"Morbidity Mortality Weekly Rep."},{"key":"B8","doi-asserted-by":"publisher","first-page":"104ra102","DOI":"10.1126\/scitranslmed.3003045","article-title":"Vitamin D is required for IFN-\u03b3\u2013mediated antimicrobial activity of human macrophages","volume":"3","author":"Fabri","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008929","article-title":"Fatty acid oxidation of alternatively activated macrophages prevents foam cell formation, but Mycobacterium tuberculosis counteracts this process via HIF-1alpha activation","volume":"16","author":"Genoula","year":"2020","journal-title":"PloS Pathog."},{"key":"B19","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/imr.12223","article-title":"Macrophage heterogeneity in tissues: phenotypic diversity and functions","volume":"262","author":"Gordon","year":"2014","journal-title":"Immunol. Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13024-018-0298-9","article-title":"New insights into the role of TREM2 in Alzheimer's disease","volume":"13","author":"Gratuze","year":"2018","journal-title":"Mol. Neurodegener"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.4049\/jimmunol.177.4.2051","article-title":"Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12","volume":"177","author":"Hamerman","year":"2006","journal-title":"J. Immunol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1111\/j.1471-4159.2009.06042.x","article-title":"A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia","volume":"109","author":"Hsieh","year":"2009","journal-title":"J. Neurochem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1038\/ni1411","article-title":"The TREM receptor family and signal integration","volume":"7","author":"Klesney-Tait","year":"2006","journal-title":"Nat. Immunol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-020-00187-z","article-title":"Pinitol prevents lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia mediated by TREM2","volume":"38","author":"Kong","year":"2020","journal-title":"Neurotoxic Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1128\/iai.02494-14","article-title":"Macrophage polarization drives granuloma outcome during Mycobacterium tuberculosis infection","volume":"83","author":"Marino","year":"2015","journal-title":"Infect. Immun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/nrmicro955","article-title":"Persistent bacterial infections: the interface of the pathogen and the host immune system","volume":"2","author":"Monack","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.molimm.2021.02.010","article-title":"Extracellular vesicles in the context of Mycobacterium tuberculosis infection","volume":"133","author":"Palacios","year":"2021","journal-title":"Mol. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1189\/jlb.0609378","article-title":"Differential polarization of alveolar macrophages and bone marrow-derived monocytes following chemically and pathogen-induced chronic lung inflammation","volume":"88","author":"Redente","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00327","article-title":"Mycobacterium tuberculosis virulent factor ESAT-6 drives macrophage differentiation toward the pro-inflammatory M1 phenotype and subsequently switches it to the anti-inflammatory M2 phenotype","volume":"8","author":"Refai","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.cell.2019.08.004","article-title":"TNF induces pathogenic programmed macrophage necrosis in tuberculosis through a mitochondrial- lysosomal-endoplasmic reticulum circuit","volume":"178","author":"Roca","year":"2019","journal-title":"Cell."},{"key":"B7","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1189\/jlb.0603252","article-title":"Interferon\u2010\u03b3: an overview of signals, mechanisms and functions","volume":"75","author":"Schroder","year":"2004","journal-title":"J. Leukocyte Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1073\/pnas.0803343106","article-title":"Efficient colonic mucosal wound repair requires Trem2 signaling","volume":"106","author":"Seno","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3520","DOI":"10.4049\/jimmunol.177.6.3520","article-title":"Cutting edge: TREM-2 attenuates macrophage activation","volume":"177","author":"Turnbull","year":"2006","journal-title":"J. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1093\/gbe\/evv035","article-title":"Insights on the emergence of Mycobacterium tuberculosis from the analysis of Mycobacterium kansasii","volume":"7","author":"Wang","year":"2015","journal-title":"Genome Biol. Evol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2509454","article-title":"Clinical significance of M1\/M2 macrophages and related cytokines in patients with spinal tuberculosis","volume":"2020","author":"Wang","year":"2020","journal-title":"Dis. Markers"},{"key":"B12","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1084\/jem.20151948","article-title":"TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques","volume":"213","author":"Wang","year":"2016","journal-title":"J. Exp. Med."},{"key":"B3","article-title":"Global tuberculosis report 2020 (World health organization)","year":"2020","journal-title":"World Health Organ"},{"key":"B28","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1084\/jem.20141732","article-title":"TREM-2 promotes macrophage survival and lung disease after respiratory viral infection","volume":"212","author":"Wu","year":"2015","journal-title":"J. Exp. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/nature12034","article-title":"Macrophage biology in development, homeostasis and disease","volume":"496","author":"Wynn","year":"2013","journal-title":"Nature"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1523\/jneurosci.2459-16.2017","article-title":"TREM2 promotes microglial survival by activating Wnt\/beta-catenin pathway","volume":"37","author":"Zheng","year":"2017","journal-title":"J. Neurosci."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1835965\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:53:07Z","timestamp":1780030387000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1835965\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":31,"alternative-id":["10.3389\/fcimb.2026.1835965"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1835965","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1835965"}}