{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:03:02Z","timestamp":1773925382259,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo\u2014Fapesp","award":["2019\/20710-9"],"award-info":[{"award-number":["2019\/20710-9"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Capes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Encephalitozoon cuniculi is an atypical, opportunistic, obligate intracellular fungal pathogen that infects vertebrates. It survives within the host by modulating the host immune response. Crotoxin (CTX), a bioactive compound isolated from the venom of Crotalus durissus terrificus, has been reported to modulate immune responses. This study evaluated the effects of CTX on the immune response of mice infected with E. cuniculi. Mice were immunosuppressed with cyclophosphamide (Cy), infected with E. cuniculi spores, and treated with a single dose of CTX on the day of experimental. The animals were euthanized on day 14 post-infection. Levels of T helper (Th1, Th2, and Th17) cytokines were measured in plasma, and macrophage and lymphocyte populations were analyzed in peritoneal lavage fluid and spleen. In addition, histopathological alterations, hepatic fungal burden, and mRNA expression levels of NLRP3 inflammasome\u2013related genes were assessed. CTX upregulated NLRP3 inflammasome expression and increased IL-18 production, while reducing fungal burden in E. cuniculi-infected mice. Moreover, CTX increased the proportions of macrophages and B cells and enhanced IFN-\u03b3 expression in CD4+ and CD8+ T lymphocytes. Collectively, these findings indicate that CTX reduces fungal load in Cy-immunosuppressed mice infected with E. cuniculi by priming the NLRP3 inflammasome complex and upregulating IL-18 production.<\/jats:p>","DOI":"10.3390\/ani16060955","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:12:26Z","timestamp":1773853946000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Crotoxin Upregulating NLRP-3 Inflammasome and IL-18 and Activating CD4+ and CD8+ Lymphocytes in Experimental Encephalitozoon cuniculi Infection"],"prefix":"10.3390","volume":"16","author":[{"suffix":"J\u00fanior","given":"Jo\u00e3o Lourival","family":"de Souza","sequence":"first","affiliation":[{"name":"Programa de Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr Bacelar 902, S\u00e3o Paulo 04026002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eluane de Luca da Silva","family":"Martins","sequence":"additional","affiliation":[{"name":"Programa de Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr Bacelar 902, S\u00e3o Paulo 04026002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-4182","authenticated-orcid":false,"given":"Anuska Marcelino","family":"Alvares Saraiva","sequence":"additional","affiliation":[{"name":"Programa de Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr Bacelar 902, S\u00e3o Paulo 04026002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3038-9902","authenticated-orcid":false,"given":"Elizabeth Christina","family":"Perez","sequence":"additional","affiliation":[{"name":"Programa de Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr Bacelar 902, S\u00e3o Paulo 04026002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4248-4990","authenticated-orcid":false,"given":"Ronalda Silva de","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Departamento de An\u00e1lises Ambientais, Divis\u00e3o de Microbiologia e Parasitologia, Companhia Ambiental do estado de S\u00e3o Paulo (CETESB), Av. Prof. Frederico Hermann J\u00fanior 345, S\u00e3o Paulo 05459900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra Coccuzzo","family":"Sampaio","sequence":"additional","affiliation":[{"name":"Departmento de Fisiopatologia, Instituto Butantan, Av. Vital Brasil, 1500, Paulo 05503900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7754-1855","authenticated-orcid":false,"given":"Rodrigo Augusto Faganholi","family":"da Silva","sequence":"additional","affiliation":[{"name":"Programa de Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr Bacelar 902, S\u00e3o Paulo 04026002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3578-3087","authenticated-orcid":false,"given":"Maria Anete","family":"Lallo","sequence":"additional","affiliation":[{"name":"Programa de Patologia Ambiental e Experimental, Universidade Paulista (UNIP), Rua Dr Bacelar 902, S\u00e3o Paulo 04026002, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","article-title":"The NLRP3 inflammasome: Molecular activation and regulation to therapeutics","volume":"19","author":"Swanson","year":"2019","journal-title":"Nat. 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