{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:16:20Z","timestamp":1790381780551,"version":"4.1.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI135005, U19AI166761"],"award-info":[{"award-number":["R01AI135005, U19AI166761"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI184340"],"award-info":[{"award-number":["T32AI184340"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Coccidioidomycosis is a pulmonary disease caused by the dimorphic fungus\n Coccidioides<\/jats:italic>\n , which is endemic to the southwestern United States and South America.\n Coccidioides<\/jats:italic>\n grows as septate hyphae in soil and forms spores that can become airborne during mechanical disruption of the soil. In the lungs, the inhaled spores develop into large multinucleated spherules, a unique morphology among medically important\n Coccidioides<\/jats:italic>\n species, and reproduce by endosporulation. A hallmark of the host immune response toward endosporulating spherules is the robust recruitment and infiltration of Ly6G\n +<\/jats:sup>\n neutrophils. However, the effectiveness of Ly6G\n +<\/jats:sup>\n neutrophils against\n Coccidioides<\/jats:italic>\n remains to be studied. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive and share an origin and many phenotypic features with neutrophils. Here, we demonstrated that Ly6G\n +<\/jats:sup>\n cells, but not Ly6C\n +<\/jats:sup>\n cells, increased lung expression of the inhibitory programmed death-ligand 1 (PD-L1) in diseased mice. The Ly6G\n +<\/jats:sup>\n PD-L1\n +<\/jats:sup>\n cells share common characteristics of granulocytic MDSCs. Bone-marrow-derived GR-1\n +<\/jats:sup>\n myeloid cells, including both Ly6G\n +<\/jats:sup>\n and Ly6C\n +<\/jats:sup>\n cells, suppressed the proliferation of CD4\n +<\/jats:sup>\n T cells after exposure to spherules. Furthermore, isolated GR-1\n +<\/jats:sup>\n cells from the lungs and spleens of\n Coccidioides<\/jats:italic>\n -infected non-protected mice also suppressed CD4\n +<\/jats:sup>\n T cell proliferation, thereby diminishing adaptive T cell responses. Adoptive transfer of GR-1\n +<\/jats:sup>\n myeloid cells isolated from the lungs of\n Coccidioides<\/jats:italic>\n -infected mice, or derived from bone marrow exposed to paraformaldehyde-killed spherules, into vaccine-protected recipients exacerbated coccidioidomycosis through the reduction of protective Th1 and Th17 responses. Altogether, we demonstrate that pulmonary infiltration of MDSC-like neutrophils, in non-vaccinated mice, play a detrimental role in coccidioidomycosis by inhibiting protective CD4\n +<\/jats:sup>\n T cell responses.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Dimorphic fungi are primary pathogens that infect both immunocompetent and immunocompromised hosts. Fungal pathogens have evolved sophisticated strategies to evade innate immune responses, which have not been well studied. Recently, myeloid-derived suppressor cells (MDSCs) have been described in the pathogenesis of several fungal infections, including\n Candida albicans<\/jats:italic>\n and\n Cryptococcus neoformans<\/jats:italic>\n . Here, we use a live-attenuated vaccine model to investigate the role of Ly6G\n +<\/jats:sup>\n myeloid cells during\n Coccidioides<\/jats:italic>\n infection in mice. We have shown that pulmonary\n Coccidioides posadasii<\/jats:italic>\n infection leads to the accumulation of programmed death-ligand 1 (PD-L1)\n +<\/jats:sup>\n Ly6G\n +<\/jats:sup>\n MDSC-like neutrophils that suppress CD4\n +<\/jats:sup>\n T cell proliferation and exacerbate disease by reducing protective Th1 and Th17 responses. Moreover, adoptive transfer of GR-1\n +<\/jats:sup>\n myeloid cells isolated from\n Coccidioides<\/jats:italic>\n -infected mice into vaccine-protected recipient mice reduced protective efficacy by increasing fungal burden and disease severity. Our data suggest that immunosuppressive Ly6G\n +<\/jats:sup>\n PD-L1\n +<\/jats:sup>\n MDSC-like neutrophils play a detrimental role by suppressing protective T cell responses in pulmonary\n Coccidioides<\/jats:italic>\n infection.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/mbio.00772-26","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T13:00:42Z","timestamp":1779973242000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Myeloid-derived suppressor cell (MDSC)-like neutrophils induced by pulmonary infection with\n Coccidioides posadasii<\/i>\n exacerbate disease by suppressing CD4\n +<\/sup>\n T cell immunity"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4389-4715","authenticated-orcid":false,"given":"Nawal","family":"Abdul-Baki","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Negron","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reimi","family":"Navarro","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Althea","family":"Campuzano","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Mendoza Barker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas D.","family":"Prather","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01kd65564","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Microbiology and Immunology, South Texas Center for Emerging Infectious Diseases, The University of Texas at San Antonio","place":["San Antonio, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8066-5763","authenticated-orcid":true,"suffix":"Jr.","given":"Paul 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