{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:49:35Z","timestamp":1793306975834,"version":"4.5.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The innate immunity, linked to macrophage polarization, plays a critical role in the progression of tuberculosis (TB) disease caused by\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic>Mtb<\/jats:italic>\n                      ) infection. Within a single patient with active pulmonary TB,\n                      <jats:italic>Mtb<\/jats:italic>\n                      infection leads to the formation of extensive lung pathology with a spectrum of morphologically and physiologically distinct TB lesions at different stages of progression, where macrophages are believed to represent varying functional phenotypes. Understanding the dynamics of macrophage polarization with identification of the cytokine network, molecular pathways, and polarizing stimuli in the lung TB lesions of patients, depending on various aspects of the host-pathogen interactions, is crucial for developing better treatment strategies, based on immune-modulatory therapeutic approaches, especially in the context of the ongoing spread of drug-resistant TB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The expression of pro-inflammatory\/anti-bacterial M1 cytokines (IFN\u03b3, TNF\u03b1, IL-1\u03b2, and IL-12) and anti-inflammatory\/immunosuppressive M2 cytokines (IL-4, IL-10, and FGF2) as well as activation of the AhR and NF-\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B pathways were estimated in an immunofluorescence assay and analyzed in relation to\n                      <jats:italic>Mtb<\/jats:italic>\n                      infection in macrophages in the\n                      <jats:italic>ex vivo<\/jats:italic>\n                      cell cultures and\/or on the histological sections obtained from various lung TB lesions of the same patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a025) with clinically active pulmonary, predominantly drug-resistant TB.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Macrophage polarization was determined by local tissue microenvironments with varying fibrosis severity but was independent of\n                      <jats:italic>Mtb<\/jats:italic>\n                      \u2019s genetic and phenotypic diversity in human lungs, the anti-TB treatment of patients before surgery and AhR signaling activity in smoker\u2019s macrophages. Pathogen control (without complete\n                      <jats:italic>Mtb<\/jats:italic>\n                      clearance) correlated with co-expression of cytokines of both cytokine types in the mixed M1\/M2-polarized macrophages and, presumably, with NF-\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B-mediated activation of smoker\u2019s alveolar macrophages in the lung TB lesions with local\/minimal fibrosis and the preserved alveoli. In contrast, suppressed macrophages (lacking cytokine production and NF-\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B-activated mediators and, in parallel, harboring higher\n                      <jats:italic>Mtb<\/jats:italic>\n                      loads) exhibited an M0-like polarization state in tuberculoma walls and extensively fibrotic lung tissues.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The host cells\u2019 inability to eradicate\n                      <jats:italic>Mtb<\/jats:italic>\n                      reflected suboptimal development of the immune responses in the patients\u2019 lungs. Defining the complexity and functional diversity of macrophage phenotypes and signaling pathways involved in the pathogen control and tissue pathology across various lung TB lesions within the same patients with pulmonary TB is essential for designing novel host-directed therapies that modulate the patients\u2019 immune responses to optimize protection against\n                      <jats:italic>Mtb<\/jats:italic>\n                      infection and prevent the pathogen transmission.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1853352","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:46:38Z","timestamp":1781239598000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Lesion-specific features of macrophage polarization contribute to Mycobacterium tuberculosis infection in the lungs of patients with pulmonary tuberculosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Elena G.","family":"Ufimtseva","sequence":"first","affiliation":[{"name":"Laboratory of Medical Biotechnology, Institute of Biochemistry, Federal Research Center of Fundamental and Translational Medicine","place":["Novosibirsk, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalya I.","family":"Eremeeva","sequence":"additional","affiliation":[{"name":"Institute of Disinfectology, F.F. Erisman Federal Scientific Center of Hygiene of the Federal Service on Surveillance for Consumer Rights Protection and Human Well-being","place":["Moscow, Russia"]},{"name":"Scientific Department, Ural Research Institute for Phthisiopulmonology, National Medical Research Center of Tuberculosis and Infectious Diseases of Ministry of Health of the Russian Federation","place":["Yekaterinburg, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey N.","family":"Skornyakov","sequence":"additional","affiliation":[{"name":"Scientific Department, Ural Research Institute for Phthisiopulmonology, National Medical Research Center of Tuberculosis and Infectious Diseases of Ministry of Health of the Russian Federation","place":["Yekaterinburg, Russia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"B1","volume-title":"Global tuberculosis report 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