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bioRxiv · 10.1101/2025.08.24.671975

Local niche-derived immunosuppressive CXCR2+ cells impair antiviral immunity

Satomi, A.·Saito, R.·Mizuno, T.·Sugishita, H.·Ukai, H.·Shichino, S.·Yanagisawa, M.·Matsushima, K.·Gotoh, Y.·Okazaki, T.
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Abstract

Symptom severity after viral infection varies among individuals, yet its mechanism remains poorly understood. We categorized mice into recovering and non-recovering groups based on body weight after infection of the same titer of vesicular stomatitis virus (VSV). We revealed that in the olfactory bulb (OB) where VSV initially expands, non-recovering mice exhibited an anti-inflammatory environment, suggesting its detrimental effect. Importantly, CXCR2+ cells resembling immunosuppressive myeloid-derived suppressor cells (MDSCs) were more abundant in the OB of non-recovering mice than in that of recovering mice after VSV infection. Depleting CXCR2+ MDSC-like cells from the brain increased inflammatory responses and the animals survival after infection. Furthermore, site-specific labeling indicated that a significant fraction of these cells in the OB originate from the skull-bone marrow (skull-BM) as well as circulation. This study reveals the lethal effects of CXCR2+ MDSC-like cells on local immune responses to viral infection, highlighting their therapeutic potential for antiviral defense.

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Satomi, A., Saito, R., Mizuno, T., Sugishita, H., Ukai, H., Shichino, S., Yanagisawa, M., Matsushima, K., Gotoh, Y., Okazaki, T.. 2025-08-27. Local niche-derived immunosuppressive CXCR2+ cells impair antiviral immunity. https://doi.org/10.1101/2025.08.24.671975

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