Myeloid-derived suppressor cell (MDSC)-like neutrophils induced by pulmonary infection with Coccidioides posadasii exacerbate disease by suppressing CD4 T cell immunity

Document Type

Article

Publication Date

5-28-2026

Publication Title

mBio

Abstract

Coccidioidomycosis is a pulmonary disease caused by the dimorphic fungus Coccidioides, which is endemic to the southwestern United States and South America. Coccidioides 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 Coccidioides species, and reproduce by endosporulation. A hallmark of the host immune response toward endosporulating spherules is the robust recruitment and infiltration of Ly6G neutrophils. However, the effectiveness of Ly6G neutrophils against Coccidioides 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 cells, but not Ly6C cells, increased lung expression of the inhibitory programmed death-ligand 1 (PD-L1) in diseased mice. The Ly6GPD-L1 cells share common characteristics of granulocytic MDSCs. Bone-marrow-derived GR-1 myeloid cells, including both Ly6G and Ly6C cells, suppressed the proliferation of CD4 T cells after exposure to spherules. Furthermore, isolated GR-1 cells from the lungs and spleens of Coccidioides-infected non-protected mice also suppressed CD4 T cell proliferation, thereby diminishing adaptive T cell responses. Adoptive transfer of GR-1 myeloid cells isolated from the lungs of Coccidioides-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 T cell responses.

First Page

1

Last Page

17

PubMed ID

42206847

Volume

17

Issue

7

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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