Compartmentalized cytokine networks and systemic immune remodeling in bovine mammary H5N1 infection.

Singh, G.; Cool, K.; Ghimire, S.; Trujillo, J. D.; Morozov, I.; Gaudreault, N. N.; Lv, H.; Jiang, K.; Li, Y.; Bumduuren, T.; McDowell, C. D.; Garcia-Sastre, A.; Wu, N. C.; Richt, J. A.

doi:10.64898/2026.03.06.710145

bioRxiv · 10.64898/2026.03.06.710145

Compartmentalized cytokine networks and systemic immune remodeling in bovine mammary H5N1 infection.

Singh, G.·Cool, K.·Ghimire, S.·Trujillo, J. D.·Morozov, I.·Gaudreault, N. N.·Lv, H.·Jiang, K.·Li, Y.·Bumduuren, T.·McDowell, C. D.·Garcia-Sastre, A.·Wu, N. C.·Richt, J. A.

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Abstract

Highly pathogenic avian influenza A H5N1 has recently expanded its mammalian host range; in 2024, genotype B3.13 emerged in U.S. dairy cattle with pronounced mammary tropism. In the past, Influenza A virus immunology has been characterized primarily in respiratory infection models, whereas this study delineates immune responses after intramammary infection. An intramammary H5N1 challenge in Jersey cows in the early dry-off period enabled integration of dose- and compartment-resolved (alveoli versus teat cistern) cytokine and chemokine profiles with peripheral leukocyte dynamics and H5/N1-specific antibody responses. Infection-induced quarter-restricted, monophasic inflammatory networks peaking at 3-7 days post-infection, coordinated peripheral myeloid expansion and IFN-{gamma}-competent lymphocyte activation, and rising antibody titers across quarters.

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Singh, G., Cool, K., Ghimire, S., Trujillo, J. D., Morozov, I., Gaudreault, N. N., Lv, H., Jiang, K., Li, Y., Bumduuren, T., McDowell, C. D., Garcia-Sastre, A., Wu, N. C., Richt, J. A.. 2026-03-06. Compartmentalized cytokine networks and systemic immune remodeling in bovine mammary H5N1 infection.. https://doi.org/10.64898/2026.03.06.710145

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