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Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    Chagas\u2019 disease is a parasitosis caused by\n                    <jats:italic>Trypanosoma cruzi<\/jats:italic>\n                    , which affects approximately 8 million people worldwide. The balance between pro- and anti-inflammatory cytokines produced during immunological responses contributes to disease prognosis and progression. Parasite tissue persistence can induce chronic inflammatory stimuli, which can cause long-term tissue injury and fibrosis. Chronic Chagas\u2019 patients exhibit increased levels of interleukin (IL)-9, an important cytokine in the regulation of inflammatory and fibrogenic processes. Data on the role of IL-9 in other pathologies are sometimes contradictory, and few studies have explored this cytokine\u2019s influence in Chagas\u2019 disease pathology. Hence, the aim of this study was to evaluate the role of IL-9 in the progression of\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    infection\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    .\n                    <jats:italic>In vitro<\/jats:italic>\n                    infection demonstrated that IL-9 reduced the number of infected cells and decreased the multiplication of intracellular amastigotes in both C2C12 myoblasts and bone marrow-derived macrophages. In myoblasts, the increased production of nitric oxide (NO) was essential for reduced parasite multiplication, whereas macrophage responses resulted in increased IL-6 and reduced TGF-\u03b2 levels, indicating that parasite growth restriction mechanisms induced by IL-9 were cell-type specific. Experimental infection of BALB\/c mice with\n                    <jats:italic>T. cruzi<\/jats:italic>\n                    trypomastigotes of the Y strain implicated a major role of IL-9 during the chronic phase, as increased Th9 and Tc9 cells were detected among splenocytes; higher levels of IL-9 in these cell populations and increased cardiac IL-9 levels were detected compared to those of uninfected mice. Moreover, rIL9 treatment decreased serum IL-12, IL-6, and IL-10 levels and cardiac TNF-\u03b1 levels, possibly attempting to control the inflammatory response. IL-9 neutralization increased cardiac fibrosis, synthesis of collagens I and III, and mastocyte recruitment in BALB\/c heart tissue during the chronic phase. In conclusion, our data showed that IL-9 reduced the invasion and multiplication of\n                    <jats:italic>T. cruzi in vitro<\/jats:italic>\n                    , in both myoblasts and macrophages, favoring disease control through cell-specific mechanisms.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , IL-9 was elevated during experimental chronic infection in BALB\/c mice, and this cytokine played a protective role in the immunopathological response during this phase by controlling cardiac fibrosis and proinflammatory cytokine production.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2021.756521","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T22:31:32Z","timestamp":1634337092000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Interleukin-9 in Immunopathology of Trypanosoma cruzi Experimental Infection"],"prefix":"10.3389","volume":"11","author":[{"given":"Nadjania Saraiva de Lira","family":"Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Mary","family":"Orikaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana Rodrigues de","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Aguiar","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Ramos","family":"Salu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Luiza Vilela","family":"Oliva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita de C\u00e1ssia","family":"Sinigaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato Arruda","family":"Mortara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01929","article-title":"The Unsolved Jigsaw Puzzle of the Immune Response in Chagas Disease","volume":"9","author":"Acevedo","year":"2018","journal-title":"Front. 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