T Cell Responses to Influenza Infections in Cattle

Abstract

Influenza viruses are major threats to global health, with potential to cause widespread disease in both humans and animals. Cattle, once considered resistant, are susceptible hosts for multiple influenza viruses, including influenza A, C and D, while no evidence currently supports infection with influenza B virus. Cattle serve not only as natural reservoirs for influenza D virus but also as emerging spillover hosts for highly pathogenic avian influenza A strains like H5N1. Their role in sustaining viral circulation, facilitating interspecies transmission, and potentially contributing to viral evolution raises significant concerns about future global outbreaks. As host immunity controls viral clearance and spread, understanding how cattle respond to influenza is essential. While most research has focused on antibody-mediated immunity, T cells play indispensable roles in controlling influenza infections by regulating antibody response, clearing infected cells, and providing long-term protection. However, bovine T cell responses to influenza remain poorly characterized. Given that most research has focused on mice and humans, this review outlines current knowledge of bovine T cell responses to influenza viruses in comparison to these well-characterized models. Cross-species comparative studies are essential to identify species-specific immunity, guide cattle vaccine development, and build predictive models to evaluate future pandemic potential.

Keywords: CD4+ T cells; CD8+ T cells; H5N1 avian influenza; T cell immunity; bovine influenza; cross-species transmission; influenza D virus; zoonotic influenza; γδ T cells.