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The severity of tuberculosis can be dependent on bacterial load and\/or lung immunopathology. Tuberculosis is aggravated by existing comorbidities such as obesity. Obesity induces metabolic dysfunction, meta inflammation and dysbiosis, which increase the prevalence of respiratory diseases and worsen immunopathology. The deficiency of IL\u20101\u03b1 (IL\u20101\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup>) induces deleterious lung monocytic inflammation and functional activation of the adaptive immune response mediated by T cells during <jats:styled-content style=\"fixed-case\"><jats:italic>M. tuberculosis<\/jats:italic><\/jats:styled-content> infection in non\u2010obese mice. Although iNOS and IFN\u2010\u03b3 have been described as protective in experimental tuberculosis, using a model of obesity induced by high\u2010fat diet, we show here an increase in iNOS\u2010expressing interstitial macrophages positively correlated with <jats:styled-content style=\"fixed-case\"><jats:italic>M. tuberculosis<\/jats:italic><\/jats:styled-content> numbers in the lungs of IL\u20101\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup> animals, followed by increased frequency of IFN\u2010\u03b3 and decreased frequency of IL\u201017\u2010producing T cells, showing that IFN\u2010\u03b3 and iNOS contribute to immunopathology and pulmonary damage. The protective effect of IL\u20101\u03b1, characterised by reduction of lung immunopathology, is dependent on IL\u201017\u2010producing CD4<jats:sup>+<\/jats:sup> cells that negatively regulate iNOS expression on macrophages. Our data provide important implications for tuberculosis with existing obesity that aggravates lung immunopathology associated with an exacerbation of IFN\u2010\u03b3\u2010producing and iNOS\u2010expressing cells.<\/jats:p>","DOI":"10.1111\/imm.13947","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:40:02Z","timestamp":1747802402000},"page":"518-533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Limitation of Deleterious <scp>iNOS<\/scp>\u2010Expressing Interstitial Macrophages Is Dependent on Protective <scp>IL<\/scp>\u20101\u03b1 and <scp>IL<\/scp>\u201017 in Tuberculosis and Existing Obesity"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7405-611X","authenticated-orcid":false,"given":"Vinicius Bottura","family":"Apolloni","sequence":"first","affiliation":[{"name":"Basic and Applied Immunology Program, Ribeirao Preto Medical School 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