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.
Show 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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