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Our study aimed to understand the role of TLR9 during the course of experimental <jats:italic>C. gattii<\/jats:italic> infection in vivo, considering that the cryptococcal DNA interaction with the receptor could contribute to host immunity even in an extremely susceptible model. We inoculated C57BL\/6 (WT) and TLR9 knock-out (TLR9<jats:sup>\u2212\/\u2212<\/jats:sup>) mice intratracheally with 10<jats:sup>4<\/jats:sup><jats:italic>C. gattii<\/jats:italic> yeast cells. TLR9<jats:sup>\u2212\/\u2212<\/jats:sup> mice had a higher mortality rate compared to WT mice and more yeast cells that had abnormal size, known as titan cells, in the lungs. TLR9<jats:sup>\u2212\/\u2212<\/jats:sup> mice also had a greater number of CFUs in the spleen and brain than WT mice, in addition to having lower levels of IFN-\u03b3 and IL-17 in the lung. With these markers of aggressive cryptococcosis, we can state that TLR9<jats:sup>\u2212\/\u2212<\/jats:sup> mice are more susceptible to <jats:italic>C. gattii<\/jats:italic>, probably due to a mechanism associated with the decrease of a Th1 and Th17-type immune response that promotes the formation of titan cells in the lungs. Therefore, our results indicate the participation of TLR9 in murine resistance to <jats:italic>C. gattii<\/jats:italic> infection.<\/jats:p>","DOI":"10.1038\/s41598-021-80959-5","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T11:11:08Z","timestamp":1610622668000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The role of Toll-like receptor 9 in a murine model of Cryptococcus gattii infection"],"prefix":"10.1038","volume":"11","author":[{"given":"Elias Barbosa","family":"da Silva-Junior","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luan","family":"Firmino-Cruz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce Cristina","family":"Guimar\u00e3es-de-Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana Valente Rodrigues","family":"De-Medeiros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"de Oliveira Nascimento","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matheus","family":"Freire-de-Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lycia","family":"de Brito-Gitirana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Morrot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose Osvaldo","family":"Previato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Mendon\u00e7a-Previato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Decote-Ricardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert Leonel","family":"de Matos Guedes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Celio Geraldo","family":"Freire-de-Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"80959_CR1","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1093\/clinids\/18.3.369","volume":"18","author":"R Rozenbaum","year":"1994","unstructured":"Rozenbaum, R. & Goncalves, A. 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