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We have previously created a subunit vaccine by encapsulating a recombinant coccidioidal Ag (rCpa1) in glucan\u2013chitin particles (GCPs) as an adjuvant-delivery system. The GCP-rCpa1 vaccine has shown to elicit a mixed Th1 and Th17 response and confers protection against pulmonary coccidioidomycosis in mice. In this study, we further delineated the vaccine-induced protective mechanisms. Depletion of IL-17A in vaccinated C57BL\/6 mice prior to challenge abrogated the protective efficacy of GCP-rCpa1 vaccine. Global transcriptome and Ingenuity Pathway Analysis of murine bone marrow\u2013derived macrophages after exposure to this vaccine revealed the upregulation of proinflammatory cytokines (TNF-\u03b1, IL-6, and IL-1\u03b2) that are associated with activation of C-type lectin receptors (CLR) Dectin-1\u2013 and Dectin-2\u2013mediated CARD9 signaling pathway. The GCP formulation of rCpa1 bound soluble Dectin-1 and Dectin-2 and triggered ITAM signaling of corresponding CLR reporter cells. Furthermore, macrophages that were isolated from Dectin-1\u2212\/\u2212, Dectin-2\u2212\/\u2212, and CARD9\u2212\/\u2212 mice significantly reduced production of inflammatory cytokines in response to the GCP-rCpa1 vaccine compared with those of wild-type mice. The GCP-rCpa1 vaccine had significantly reduced protective efficacy in Dectin-1\u2212\/\u2212, Dectin-2\u2212\/\u2212, and CARD9\u2212\/\u2212 mice that showed decreased acquisition of Th cells in Coccidioides-infected lungs compared with vaccinated wild-type mice, especially Th17 cells. Collectively, we conclude that the GCP-rCpa1 vaccine stimulates a robust Th17 immunity against Coccidioides infection through activation of the CARD9-associated Dectin-1 and Dectin-2 signal pathways.<\/jats:p>","DOI":"10.4049\/jimmunol.1900793","type":"journal-article","created":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T19:45:15Z","timestamp":1588362315000},"page":"3296-3306","source":"Crossref","is-referenced-by-count":34,"title":["CARD9-Associated Dectin-1 and Dectin-2 Are Required for Protective Immunity of a Multivalent Vaccine against <i>Coccidioides posadasii<\/i> Infection"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-7113","authenticated-orcid":false,"given":"Althea","family":"Campuzano","sequence":"first","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-1861","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4202-4556","authenticated-orcid":false,"given":"Gary R","family":"Ostroff","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, Department of Medicine, University of Massachusetts Medical School , Worcester, MA 01605"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2344-1354","authenticated-orcid":false,"given":"Lucas","family":"dos Santos Dias","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel","family":"W\u00fcthrich","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce S","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics , Madison, WI 53792"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-3366","authenticated-orcid":false,"given":"Jieh-Juen","family":"Yu","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4854-9839","authenticated-orcid":false,"given":"Humberto H","family":"Lara","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1992-3270","authenticated-orcid":false,"given":"Jose L","family":"Lopez-Ribot","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1091-3420","authenticated-orcid":false,"given":"Chiung-Yu","family":"Hung","sequence":"additional","affiliation":[{"name":"South Texas Center for Emerging Infectious Diseases, Department of Biology, The University of Texas at San Antonio , San Antonio, TX 78249"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2025030417512205400_r1","first-page":"185","article-title":"Coccidioidomycosis: epidemiology","volume":"5","author":"Brown","year":"2013","journal-title":"Clin. 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