{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:33Z","timestamp":1787016573152,"version":"build-2736575974"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI071118"],"award-info":[{"award-number":["AI071118"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI114762"],"award-info":[{"award-number":["AI114762"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Coccidioidomycosis is a potentially life-threatening respiratory disease which is endemic to the southwestern United States and arid regions of Central and South America. It is responsible for approximately 150,000 infections annually in the United States alone. Almost every human organ has been reported to harbor parasitic cells of\n                    <jats:named-content content-type=\"genus-species\">Coccidioides<\/jats:named-content>\n                    spp. in collective cases of the disseminated form of this mycosis. Current understanding of the mechanisms of protective immunity against lung infection has been largely derived from murine models of pulmonary coccidioidomycosis. However, little is known about the nature of the host response to\n                    <jats:named-content content-type=\"genus-species\">Coccidioides<\/jats:named-content>\n                    in extrapulmonary tissue. Primary subcutaneous coccidioidal infection is rare but has been reported to result in disseminated disease. Here, we show that activation of MyD88 and Card9 signal pathways are required for resistance to\n                    <jats:named-content content-type=\"genus-species\">Coccidioides<\/jats:named-content>\n                    infection following subcutaneous challenge of C57BL\/6 mice, which correlates with earlier findings of the protective response to pulmonary infection.\n                    <jats:italic>MyD88<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and\n                    <jats:italic>Card9<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice recruited reduced numbers of T cells, B cells, and neutrophils to the\n                    <jats:named-content content-type=\"genus-species\">Coccidioides<\/jats:named-content>\n                    -infected hypodermis compared to wild-type mice; however, neutrophils were dispensable for resistance to skin infection. Further studies have shown that gamma interferon (IFN-\u03b3) production and activation of Th1 cells characterize resistance to subcutaneous infection. Furthermore, activation of a phagosomal enzyme, inducible nitric oxide synthase, which is necessary for NO production, is a requisite for fungal clearance in the hypodermis. Collectively, our data demonstrate that MyD88- and Card9-mediated IFN-\u03b3 and nitric oxide production is essential for protection against subcutaneous\n                    <jats:named-content content-type=\"genus-species\">Coccidioides<\/jats:named-content>\n                    infection.\n                  <\/jats:p>","DOI":"10.1128\/iai.01066-15","type":"journal-article","created":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T23:29:23Z","timestamp":1454974163000},"page":"1166-1175","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Card9- and MyD88-Mediated Gamma Interferon and Nitric Oxide Production Is Essential for Resistance to Subcutaneous Coccidioides posadasii Infection"],"prefix":"10.1128","volume":"84","author":[{"given":"Chiung-Yu","family":"Hung","sequence":"first","affiliation":[{"name":"Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Castro-Lopez","sequence":"additional","affiliation":[{"name":"Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry T.","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Biology and South Texas Center for Emerging Infectious Diseases, University of Texas, San Antonio, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S34434"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu681"},{"key":"e_1_3_2_4_2","first-page":"363","volume-title":"Molecular principles of fungal pathogenesis","author":"Cole G","year":"2006","unstructured":"Cole G, Xue J, Borra P, KS, Borra R, Tarcha E, Schaller R, Yu J-J, Hung C-Y. 2006. Virulence mechanisms of Coccidioides, p 363\u2013391. In Heitman J, Filler S, Edwards J, Mitchell A (ed), Molecular principles of fungal pathogenesis. ASM Press, Washington, DC."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780410001687349"},{"key":"e_1_3_2_6_2","first-page":"356","volume-title":"Medical mycology","author":"Kwon-Chung KJ","year":"1992","unstructured":"Kwon-Chung KJ, Bennett JE. 1992. Coccidioidomycosis, p 356\u2013396. In Cann C (ed), Medical mycology. Lea & Febiger, Philadelphia, PA."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-013-0352-2"},{"key":"e_1_3_2_8_2","first-page":"653","article-title":"Coccidioidomycosis; a study of 95 cases of the disseminated type with special reference to the pathogenesis of the disease","volume":"99","author":"Forbus WD","year":"1946","unstructured":"Forbus WD, Bestebreurtje AM. 1946. 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