{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:10:45Z","timestamp":1779894645637,"version":"3.53.1"},"reference-count":126,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,25]],"date-time":"2024-02-25T00:00:00Z","timestamp":1708819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases","award":["U19AI166059"],"award-info":[{"award-number":["U19AI166059"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["R01AI137418"],"award-info":[{"award-number":["R01AI137418"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["NIH R01 AI135005"],"award-info":[{"award-number":["NIH R01 AI135005"]}]},{"name":"National Institute of Allergy and Infectious Diseases","award":["U19AI166761"],"award-info":[{"award-number":["U19AI166761"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Coccidioidomycosis is an important fungal disease that is found in many desert regions of the western hemisphere. The inhaled organisms are highly pathogenic, but only half of infected, immunologically intact people develop symptomatic pneumonia; most symptomatic infections resolve spontaneously, although some resolve very slowly. Furthermore, second infections are very rare and natural immunity after infection is robust. Therefore, the host response to this organism is very effective at resolving the infection in most cases and immunizing to prevent second infections. People who are immunocompromised are much more likely to develop disseminated infection. This is a comprehensive review of the innate and acquired immune responses to Coccidioides spp., the genetics of resistance to severe infection, and the search for an effective vaccine.<\/jats:p>","DOI":"10.3390\/jof10030173","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T03:34:04Z","timestamp":1708918444000},"page":"173","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Host Response to Coccidioidomycosis"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7908-7302","authenticated-orcid":false,"given":"Theo N.","family":"Kirkland","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, San Diego School of Medicine, University of California, San Diego, CA 92093, USA"},{"name":"Department of Pathology, San Diego School of Medicine, University of California, San Diego, CA 92093, USA"}],"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 Disease, Department of Molecular Microbiology and Immunology, University of Texas at San Antonio, San Antonio, TX 78249, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa F.","family":"Shubitz","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0906-7538","authenticated-orcid":false,"given":"Sinem","family":"Beyhan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, San Diego School of Medicine, University of California, San Diego, CA 92093, USA"},{"name":"Department of Infectious Diseases, J. Craig Venter Institute, La Jolla, CA 92037, USA"},{"name":"Infectious Diseases Section, VA Healthcare San Diego, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9230-5279","authenticated-orcid":false,"given":"Joshua","family":"Fierer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, San Diego School of Medicine, University of California, San Diego, CA 92093, USA"},{"name":"Department of Pathology, San Diego School of Medicine, University of California, San Diego, CA 92093, USA"},{"name":"Infectious Diseases Section, VA Healthcare San Diego, San Diego, CA 92161, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.2105\/AJPH.30.6.600","article-title":"Epidemiology of Acute Coccidioidomycosis with Erythema Nodosum (\u201cSan Joaquin\u201d or \u201cValley Fever\u201d)","volume":"30","author":"Smith","year":"1940","journal-title":"Am. J. Public Health Nations Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1128\/CMR.00005-13","article-title":"Recent advances in our understanding of the environmental, epidemiological, immunological, and clinical dimensions of coccidioidomycosis","volume":"26","author":"Nguyen","year":"2013","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1426","DOI":"10.1080\/21505594.2018.1509667","article-title":"Coccidioides immitis and posadasii; A review of their biology, genomics, pathogenesis, and host immunity","volume":"9","author":"Kirkland","year":"2018","journal-title":"Virulence"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kirkland, T.N., Stevens, D.A., Hung, C.Y., Beyhan, S., Taylor, J.W., Shubitz, L.F., Duttke, S.H., Heidari, A., Johnson, R.H., and Deresinski, S.C. (2022). Coccidioides Species: A Review of Basic Research: 2022. J. Fungi, 8.","DOI":"10.3390\/jof8080859"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1080\/21505594.2019.1589363","article-title":"The mysterious desert dwellers: Coccidioides immitis and Coccidioides posadasii, causative fungal agents of coccidioidomycosis","volume":"10","author":"Kollath","year":"2019","journal-title":"Virulence"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1093\/mmy\/myy146","article-title":"A review of innate and adaptive immunity to coccidioidomycosis","volume":"57","author":"Hung","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1128\/CMR.17.4.804-839.2004","article-title":"Coccidioidomycosis: Host response and vaccine development","volume":"17","author":"Cox","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.mib.2020.10.003","article-title":"The first line of defense: Effector pathways of anti-fungal innate immunity","volume":"58","author":"Ward","year":"2020","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kirkland, T.N., and Fierer, J. (2020). Innate Immune Receptors and Defense Against Primary Pathogenic Fungi. Vaccines, 8.","DOI":"10.3390\/vaccines8020303"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00112-19","DOI":"10.1128\/CMR.00112-19","article-title":"Early Events in Coccidioidomycosis","volume":"33","author":"Donovan","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.immuni.2009.06.004","article-title":"Approaching the asymptote: 20 years later","volume":"30","author":"Medzhitov","year":"2009","journal-title":"Immunity"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ward, R.A., Thompson, G.R., Villani, A.C., Li, B., Mansour, M.K., Wuethrich, M., Tam, J.M., Klein, B.S., and Vyas, J.M. (2021). The Known Unknowns of the Immune Response to Coccidioides. J. Fungi, 7.","DOI":"10.3390\/jof7050377"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e159491","DOI":"10.1172\/jci.insight.159491","article-title":"Immunogenetics associated with severe coccidioidomycosis","volume":"7","author":"Hsu","year":"2022","journal-title":"JCI Insight"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Margolis, D.A., Viriyakosol, S., Fierer, J., and Kirkland, T.N. (2011). The role of reactive oxygen intermediates in experimental coccidioidomycois in mice. BMC Microbiol., 11.","DOI":"10.1186\/1471-2180-11-71"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1465-9921-5-28","article-title":"Coccidioides posadasii infection alters the expression of surfactant proteins SP-A and SP-D","volume":"5","author":"Awasthi","year":"2004","journal-title":"Respir. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1128\/iai.21.3.862-865.1978","article-title":"Chemotaxigenic activity of extracts from the mycelial and spherule phases of Coccidioides immitis for human polymorphonuclear leukocytes","volume":"21","author":"Galgiani","year":"1978","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, C.Y., Thompson, G.R., Hastey, C.J., Hodge, G.C., Lunetta, J.M., Pappagianis, D., and Heinrich, V. (2015). Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129522"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/infdis\/149.3.404","article-title":"Human polymorphonuclear-leukocyte inhibition of incorporation of chitin precursors into mycelia of Coccidioides immitis","volume":"149","author":"Galgiani","year":"1984","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/infdis\/153.2.217","article-title":"Inhibition of different phases of Coccidioides immitis by human neutrophils or hydrogen peroxide","volume":"153","author":"Galgiani","year":"1986","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1093\/infdis\/153.5.933","article-title":"Influence of fungal surface components on the interaction of Coccidioides immitis with polymorphonuclear neutrophils","volume":"153","author":"Frey","year":"1986","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/infdis\/151.5.890","article-title":"In Vitro Effect of Phagocyte Cationic Peptides on Coccidioides immitis","volume":"151","author":"Segal","year":"1985","journal-title":"J. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00883-19","DOI":"10.1128\/IAI.00883-19","article-title":"Interleukin-8 Receptor 2 (IL-8R2)-Deficient Mice Are More Resistant to Pulmonary Coccidioidomycosis than Control Mice","volume":"89","author":"Carlin","year":"2020","journal-title":"Infect. Immun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1128\/IAI.01579-13","article-title":"Interleukin-1 receptor but not Toll-like receptor 2 is essential for MyD88-dependent Th17 immunity to Coccidioides infection","volume":"82","author":"Hung","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.chom.2012.04.005","article-title":"Dendritic cells in antifungal immunity and vaccine design","volume":"11","author":"Roy","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Marakalala, M.J., Martinez, F.O., Pl\u00fcddemann, A., and Gordon, S. (2018). Macrophage Heterogeneity in the Immunopathogenesis of Tuberculosis. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01028"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1002\/eji.202149513","article-title":"Dendritic cell functions in vivo: A user\u2019s guide to current and next- generation mutant mouse models","volume":"52","author":"Dalod","year":"2022","journal-title":"Eur. J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1128\/iai.34.2.347-353.1981","article-title":"Role of lymphocytes in macrophage-induced killing of Coccidioides immitis in vitro","volume":"34","author":"Beaman","year":"1981","journal-title":"Infect. Immun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1128\/iai.39.3.1201-1207.1983","article-title":"Activation of macrophages by lymphokines: Enhancement of phagosome-lysosome fusion and killing of Coccidioides immitis","volume":"39","author":"Beaman","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Diep, A.L., Tejeda-Garibay, S., Miranda, N., and Hoyer, K.K. (2021). Macrophage and Dendritic Cell Activation and Polarization in Response to Coccidioidesposadasii Infection. J. Fungi, 7.","DOI":"10.3390\/jof7080630"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.4049\/jimmunol.169.7.3876","article-title":"The beta-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte\/macrophage and neutrophil lineages","volume":"169","author":"Taylor","year":"2002","journal-title":"J. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e00597-12","DOI":"10.1128\/mBio.00597-12","article-title":"Dectin-1 is required for resistance to coccidioidomycosis in mice","volume":"4","author":"Viriyakosol","year":"2013","journal-title":"mBio"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/gene.2008.23","article-title":"Susceptibility to Coccidioides species in C57BL\/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a)","volume":"9","author":"Viriyakosol","year":"2008","journal-title":"Genes Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.4049\/jimmunol.1900793","article-title":"CARD9-Associated Dectin-1 and Dectin-2 Are Required for Protective Immunity of a Multivalent Vaccine against Coccidioides posadasii Infection","volume":"204","author":"Campuzano","year":"2020","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1128\/iai.40.3.912-916.1983","article-title":"Inbred Mouse Strains Differ in Resistance to Lethal Coccidioides immitis Infection","volume":"40","author":"Kirkland","year":"1983","journal-title":"Infect. Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.4049\/jimmunol.176.9.5513","article-title":"Expression of functionally different dectin-1 isoforms by murine macrophages","volume":"176","author":"Heinsbroek","year":"2006","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Powell, D.A., Hsu, A.P., Butkiewicz, C.D., Trinh, H.T., Frelinger, J.A., Holland, S.M., Galgiani, J.N., and Shubitz, L.F. (2021). Vaccine Protection of Mice With Primary Immunodeficiencies Against Disseminated Coccidioidomycosis. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.790488"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1128\/IAI.01355-13","article-title":"Neither dectin-2 nor the mannose receptor is required for resistance to Coccidioides immitis in mice","volume":"82","author":"Viriyakosol","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1128\/IAI.74.4.2415-2422.2006","article-title":"Spherules Derived from Coccidioides posadasii Promote Human Dendritic Cell Maturation and Activation","volume":"74","author":"Dionne","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1128\/IAI.73.4.2554-2555.2005","article-title":"The Mannose Receptor Mediates the Cellular Immune Response in Human Coccidioidomycosis","volume":"73","author":"Ampel","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.4049\/jimmunol.1302314","article-title":"C-type lectin receptors differentially induce th17 cells and vaccine immunity to the endemic mycosis of North America","volume":"192","author":"Wang","year":"2014","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1128\/IAI.73.3.1553-1560.2005","article-title":"Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on TLR2 and dectin-1","volume":"73","author":"Viriyakosol","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00028-18","DOI":"10.1128\/IAI.00028-18","article-title":"Myeloid Differentiation Factor 88 and Interleukin-1R1 Signaling Contribute to Resistance to Coccidioides immitis","volume":"86","author":"Viriyakosol","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1128\/EC.00122-15","article-title":"Differences in Host Innate Responses among Coccidioides Isolates in a Murine Model of Pulmonary Coccidioidomycosis","volume":"14","author":"Lewis","year":"2015","journal-title":"Eukaryot. Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1128\/IAI.01066-15","article-title":"Card9- and MyD88-Mediated Gamma Interferon and Nitric Oxide Production Is Essential for Resistance to Subcutaneous Coccidioides posadasii Infection","volume":"84","author":"Hung","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Higgins Keppler, E.A., Van Dyke, M.C.C., Mead, H.L., Lake, D.F., Magee, D.M., Barker, B.M., and Bean, H.D. (2023). Volatile Metabolites in Lavage Fluid Are Correlated with Cytokine Production in a Valley Fever Murine Model. J. Fungi, 9.","DOI":"10.3390\/jof9010115"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"548","DOI":"10.4049\/jimmunol.135.1.548","article-title":"Genetic control of resistance to Coccidioides immitis: A single gene that is expressed in spleen cells determines resistance","volume":"135","author":"Kirkland","year":"1985","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1128\/iai.56.1.13-17.1988","article-title":"Induction and expression of cell-mediated immune responses in inbred mice infected with Coccidioides immitis","volume":"56","author":"Cox","year":"1988","journal-title":"Infect. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1128\/iai.64.9.3609-3613.1996","article-title":"Interleukin-12 regulation of host defenses against Coccidioides immitis","volume":"64","author":"Magee","year":"1996","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4397","DOI":"10.1128\/IAI.66.9.4397-4402.1998","article-title":"Importance of interleukin-10 in genetic susceptibility of mice to Coccidioides immitis","volume":"66","author":"Fierer","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1128\/IAI.67.6.2916-2919.1999","article-title":"Genes influencing resistance to Coccidioides immitis and the interleukin-10 response map to chromosomes 4 and 6 in mice","volume":"67","author":"Fierer","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"43818","DOI":"10.1074\/jbc.M107715200","article-title":"Characterization of the human beta-glucan receptor and its alternatively spliced isoforms","volume":"276","author":"Willment","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Woelk, C.H., Zhang, J.X., Walls, L., Viriyakosol, S., Singhania, A., Kirkland, T.N., and Fierer, J. (2012). Factors regulated by interferon gamma and hypoxia-inducible factor 1A contribute to responses that protect mice from Coccidioides immitis infection. BMC Microbiol., 12.","DOI":"10.1186\/1471-2180-12-218"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1086\/605532","article-title":"Refractory disseminated coccidioidomycosis and mycobacteriosis in interferon-gamma receptor 1 deficiency","volume":"49","author":"Vinh","year":"2009","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1093\/cid\/ciq215","article-title":"Interleukin-12 Receptor 1 Deficiency Predisposing to Disseminated Coccidioidomycosis","volume":"52","author":"Vinh","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1016\/j.jaci.2013.01.052","article-title":"Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis","volume":"131","author":"Sampaio","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/infdis\/jiaa419","article-title":"A Chronic Murine Disease Model of Coccidioidomycosis Using Coccidioides posadasii, strain 1038","volume":"223","author":"Shubitz","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1093\/infdis\/171.4.961","article-title":"Coccidioidomycosis among persons with AIDS in the united states","volume":"171","author":"Jones","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S56","DOI":"10.1093\/mmy\/myy019","article-title":"Coccidioidomycosis in selected immunosuppressed hosts","volume":"57","author":"Blair","year":"2019","journal-title":"Med. Mycol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3201\/eid0203.960305","article-title":"Coccidioidomycosis: A reemerging infectious disease","volume":"2","author":"Kirkland","year":"1996","journal-title":"Emerg. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e3814","DOI":"10.1093\/cid\/ciaa1154","article-title":"Natural History of Disseminated Coccidioidomycosis: Examination of the Veterans Affairs-Armed Forces Database","volume":"73","author":"Bays","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"63","DOI":"10.4065\/mcp.2010.0423","article-title":"Coccidioidomycosis in African Americans","volume":"86","author":"Ruddy","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1086\/319203","article-title":"Risk factors for severe pulmonary and disseminated coccidioidomycosis: Kern County, California, 1995\u20131996","volume":"32","author":"Rosenstein","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"70","DOI":"10.3201\/eid2101.140836","article-title":"Rates and risk factors for Coccidioidomycosis among prison inmates, California, USA, 2011","volume":"21","author":"Wheeler","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3201\/eid0505.990508","article-title":"Influence of host genetics on the severity of coccidioidomycosis","volume":"5","author":"Louie","year":"1999","journal-title":"Emerg. Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1096\/fj.08-120006","article-title":"Duox maturation factors form cell surface complexes with Duox affecting the specificity of reactive oxygen species generation","volume":"23","author":"Morand","year":"2009","journal-title":"FASEB J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-1-4614-4726-9_3","article-title":"Invasive fungal infections in patients with chronic granulomatous disease","volume":"764","author":"Henriet","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.micpath.2011.08.003","article-title":"Absence of phagocyte NADPH oxidase 2 leads to severe inflammatory response in lungs of mice infected with Coccidioides","volume":"51","author":"Gonzalez","year":"2011","journal-title":"Microb. Pathog."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.micpath.2011.03.013","article-title":"Nitric oxide synthase activity has limited influence on the control of Coccidioides infection in mice","volume":"51","author":"Gonzalez","year":"2011","journal-title":"Microb. Pathog."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1128\/IAI.01985-05","article-title":"High Levels of Interleukin-10 Impair Resistance to Pulmonary Coccidioidomycosis in Mice in Part through Control of Nitric Oxide Synthase 2 Expression","volume":"74","author":"Jimenez","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1001\/jama.1956.02960420026008","article-title":"Pattern of 39,500 serologic tests in coccidioidomycosis","volume":"160","author":"Smith","year":"1956","journal-title":"J. Am. Med. Assoc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1128\/iai.47.3.814-821.1985","article-title":"Systemic Coccidioides immitis infection in nude and beige mice","volume":"47","author":"Clemons","year":"1985","journal-title":"Infect. Immun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1128\/iai.23.3.681-685.1979","article-title":"Mechanisms of resistance to infection with Coccidioides immitis in mice","volume":"23","author":"Beaman","year":"1979","journal-title":"Infect. Immun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.4049\/jimmunol.95.6.1048","article-title":"Enhancement of immune responses in mice by a booster injection of Coccidioides spherules","volume":"95","author":"Kong","year":"1965","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1128\/IAI.73.10.7011-7013.2005","article-title":"Role of B cells in vaccine-induced immunity against coccidioidomycosis","volume":"73","author":"Magee","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1086\/502972","article-title":"Both CD4+ and CD8+ T cells can medicate vaccine-induced protection against Coccidioides immitis infection in mice","volume":"193","author":"Fierer","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.4049\/jimmunol.136.7.2348","article-title":"Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins","volume":"136","author":"Mosmann","year":"1986","journal-title":"J. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kara, E.E., Comerford, I., Fenix, K.A., Bastow, C.R., Gregor, C.E., McKenzie, D.R., and McColl, S.R. (2014). Tailored immune responses: Novel effector helper T cell subsets in protective immunity. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003905"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.vaccine.2005.07.092","article-title":"Molecular and cellular mechanisms of protective immunity to coccidioidomycosis","volume":"24","author":"Kirkland","year":"2006","journal-title":"Vaccine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.1128\/IAI.00459-09","article-title":"A genetically engineered live attenuated vaccine of Coccidioides posadasii protects BALB\/c mice against coccidioidomycosis","volume":"77","author":"Xue","year":"2009","journal-title":"Infect. Immun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1172\/JCI43984","article-title":"Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice","volume":"121","author":"Gern","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4511","DOI":"10.1128\/IAI.05726-11","article-title":"Vaccine immunity to coccidioidomycosis occurs by early activation of three signal pathways of T helper cell response (Th1, Th2, and Th17)","volume":"79","author":"Hung","year":"2011","journal-title":"Infect. Immun."},{"key":"ref_82","first-page":"330","article-title":"The use of coccidioidin","volume":"57","author":"Smith","year":"1948","journal-title":"Am. Rev. Tuberc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1086\/516115","article-title":"Prediction of relapse after treatment of coccidioidomycosis","volume":"25","author":"Oldfield","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1093\/mmy\/myz099","article-title":"Coccidioides (spherulin) skin testing in patients with pulmonary coccidioidomycosis in an endemic regiondagger","volume":"58","author":"Mafi","year":"2020","journal-title":"Med. Mycol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.4049\/jimmunol.102.5.1284","article-title":"Coccidioidin delayed hypersensitivity: Skin test and in vitro lymphocyte reactivities","volume":"102","author":"Zweiman","year":"1969","journal-title":"J. Immunol."},{"key":"ref_86","first-page":"937","article-title":"In vivo and in vitro cell-mediated responses in coccidioidomycosis. I. Immumologic responses of persons with primary, asymptomatic infections","volume":"114","author":"Cox","year":"1976","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1128\/iai.15.3.751-755.1977","article-title":"In vitro lymphocyte responses of coccidioidin skin test-positive and -negative persons to coccidioidin, spherulin, and a coccidioides cell wall antigen","volume":"15","author":"Cox","year":"1977","journal-title":"Infect. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/infdis\/165.4.710","article-title":"In vitro assessment of cellular immunity in human coccidioidomycosis: Relationship between dermal hypersensitivity, lymphocyte transformation, and lymphokine production by peripheral blood mononuclear cells from healthy adults","volume":"165","author":"Ampel","year":"1992","journal-title":"J. Infect. Dis."},{"key":"ref_89","first-page":"700","article-title":"Preliminary evaluation of whole-blood gamma interferon release for clinical assessment of cellular immunity in patients with active coccidioidomycosis","volume":"12","author":"Ampel","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1093\/infdis\/174.2.440","article-title":"Cytokine production by peripheral blood mononuclear cells in human coccidioidomycosis","volume":"174","author":"Corry","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/mmy.39.4.315.320","article-title":"Assessment of the human cellular immune response to T27K, a coccidioidal antigen preparation, by flow cytometry of whole blood","volume":"39","author":"Ampel","year":"2001","journal-title":"Med. Mycol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e00065-18","DOI":"10.1128\/mSphere.00065-18","article-title":"Ex Vivo Cytokine Release, Determined by a Multiplex Cytokine Assay, in Response to Coccidioidal Antigen Stimulation of Whole Blood among Subjects with Recently Diagnosed Primary Pulmonary Coccidioidomycosis","volume":"3","author":"Ampel","year":"2018","journal-title":"mSphere"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.jaci.2018.10.022","article-title":"Elevated regulatory T cells at diagnosis of Coccidioides infection associates with chronicity in pediatric patients","volume":"142","author":"Davini","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3923","DOI":"10.1128\/IAI.73.7.3923-3928.2005","article-title":"Cellular immune suppressor activity resides in lymphocyte cell clusters adjacent to granulomata in human coccidioidomycosis","volume":"73","author":"Li","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1056\/NEJMoa2000024","article-title":"Disseminated Coccidioidomycosis Treated with Interferon-gamma and Dupilumab","volume":"382","author":"Tsai","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1128\/iai.25.1.440-445.1979","article-title":"Immunization of mice against coccidioidomycosis with a subcellular vaccine","volume":"25","author":"Pappagianis","year":"1979","journal-title":"Infect. Immun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1128\/IAI.66.5.2342-2345.1998","article-title":"Protection against lethal murine coccidioidomycosis by a soluble vaccine from spherules","volume":"66","author":"Zimmermann","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1196\/annals.1406.016","article-title":"Characteristics of the protective subcellular coccidioidal T27K vaccine","volume":"1111","author":"Johnson","year":"2007","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"218","DOI":"10.4049\/jimmunol.87.2.218","article-title":"Immunogenicity of spherule-endospore vaccines of Coccidioides immitis for mice","volume":"87","author":"Levine","year":"1961","journal-title":"J. Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/oxfordjournals.aje.a113776","article-title":"Immunologic responsiveness and safety associated with the Coccidioides immitis spherule vaccine in volunteers of white, black, and Filipino ancestry","volume":"119","author":"Williams","year":"1984","journal-title":"Am. J. Epidemiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1164\/ajrccm\/148.3.656","article-title":"Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans. The Valley Fever Vaccine Study Group","volume":"148","author":"Pappagianis","year":"1993","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/00362177185190401","article-title":"Immunization of mice with induced mutants of Coccidioides immitis. I. Characterization of mutants and preliminary studies of their use as viable vaccines","volume":"9","author":"Walch","year":"1971","journal-title":"Sabouraudia"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1016\/j.vaccine.2016.08.078","article-title":"Preclinical identification of vaccine induced protective correlates in human leukocyte antigen expressing transgenic mice infected with Coccidioides posadasii","volume":"34","author":"Hurtgen","year":"2016","journal-title":"Vaccine"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1128\/IAI.00633-16","article-title":"A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection","volume":"84","author":"Narra","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3375","DOI":"10.1016\/j.vaccine.2018.04.026","article-title":"Viable spores of Coccidioides posadasii Deltacps1 are required for vaccination and provide long lasting immunity","volume":"36","author":"Shubitz","year":"2018","journal-title":"Vaccine"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6894","DOI":"10.1016\/j.vaccine.2021.10.029","article-title":"\u0394cps1 vaccine protects dogs against experimentally induced coccidioidomycosis","volume":"39","author":"Shubitz","year":"2021","journal-title":"Vaccine"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Mandel, M.A., Beyhan, S., Voorhies, M., Shubitz, L.F., Galgiani, J.N., Orbach, M.J., and Sil, A. (2022). The WOPR family protein Ryp1 is a key regulator of gene expression, development, and virulence in the thermally dimorphic fungal pathogen Coccidioides posadasii. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1009832"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Beyhan, S., Gutierrez, M., Voorhies, M., and Sil, A. (2013). A Temperature-Responsive Network Links Cell Shape and Virulence Traits in a Primary Fungal Pathogen. PLoS Biol., 11.","DOI":"10.1371\/journal.pbio.1001614"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1128\/IAI.68.2.584-593.2000","article-title":"A major cell surface antigen of Coccidioides immitis which elicits both humoral and cellular immune responses","volume":"68","author":"Hung","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1128\/IAI.67.6.2935-2940.1999","article-title":"Resistance to Coccidioides immitis in mice after immunization with recombinant protein or a DNA vaccine of a proline-rich antigen","volume":"67","author":"Abuodeh","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1128\/IAI.66.8.3519-3522.1998","article-title":"Evaluation of the proline-rich antigen of Coccidioides immitis as a vaccine candidate in mice","volume":"66","author":"Kirkland","year":"1998","journal-title":"Infect. Immun."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1016\/j.vaccine.2006.04.002","article-title":"Improved protection of mice against lethal respiratory infection with Coccidioides posadasii using two recombinant antigens expressed as a single protein","volume":"24","author":"Shubitz","year":"2006","journal-title":"Vaccine"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1128\/IAI.67.2.630-635.1999","article-title":"Genetic vaccination against Coccidioides immitis: Comparison of vaccine efficacy of recombinant antigen 2 and antigen 2 cDNA","volume":"67","author":"Jiang","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1128\/IAI.67.11.5848-5853.1999","article-title":"Coadministration of interleukin 12 expression vector with antigen 2 cDNA enhances induction of protective immunity against Coccidioides immitis","volume":"67","author":"Jiang","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.chom.2015.02.009","article-title":"Calnexin induces expansion of antigen-specific CD4(+) T cells that confer immunity to fungal ascomycetes via conserved epitopes","volume":"17","author":"Brandhorst","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1128\/IAI.74.1.516-527.2006","article-title":"A recombinant aspartyl protease of Coccidioides posadasii induces protection against pulmonary coccidioidomycosis in mice","volume":"74","author":"Tarcha","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1128\/IAI.00566-12","article-title":"Construction and evaluation of a novel recombinant T cell epitope-based vaccine against Coccidioidomycosis","volume":"80","author":"Hurtgen","year":"2012","journal-title":"Infect. Immun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1084\/jem.186.10.1623","article-title":"CpG oligodeoxynucleotides act as adjuvants that switch on T helper 1 (Th1) immunity","volume":"186","author":"Chu","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e00070-18","DOI":"10.1128\/IAI.00070-18","article-title":"Glucan-Chitin Particles Enhance Th17 Response and Improve Protective Efficacy of a Multivalent Antigen (rCpa1) against Pulmonary Coccidioides posadasii Infection","volume":"86","author":"Hung","year":"2018","journal-title":"Infect. Immun."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Kirkland, T.N. (2016). The Quest for a Vaccine Against Coccidioidomycosis: A Neglected Disease of the Americas. J. Fungi, 2.","DOI":"10.20944\/preprints201612.0076.v1"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4359","DOI":"10.1016\/S0264-410X(03)00485-7","article-title":"Identification of a protective antigen of Coccidioides immitis by expression library immunization","volume":"21","author":"Ivey","year":"2003","journal-title":"Vaccine"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5777","DOI":"10.1128\/IAI.00807-07","article-title":"Evaluation of two homologous proline-rich proteins of Coccidioides posadasii as candidate vaccines against coccidioidomycosis","volume":"75","author":"Herr","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"3010","DOI":"10.1128\/IAI.71.6.3010-3019.2003","article-title":"A recombinant beta-1,3-glucanosyltransferase homolog of Coccidioides posadasii protects mice against coccidioidomycosis","volume":"71","author":"Delgado","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e85","DOI":"10.1038\/cti.2016.22","article-title":"Toll-like receptors: The swiss army knife of immunity and vaccine development","volume":"5","author":"Dowling","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"ofad597","DOI":"10.1093\/ofid\/ofad597","article-title":"A Clinicopathological Categorization System for Clinical Research in Coccidioidomycosis","volume":"10","author":"Krogstad","year":"2023","journal-title":"Open Forum Infect. Dis."}],"container-title":["Journal of Fungi"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2309-608X\/10\/3\/173\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:04:32Z","timestamp":1760105072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2309-608X\/10\/3\/173"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,25]]},"references-count":126,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["jof10030173"],"URL":"https:\/\/doi.org\/10.3390\/jof10030173","relation":{},"ISSN":["2309-608X"],"issn-type":[{"value":"2309-608X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,25]]}}}