T-cell-mediated immunity in mastitis: pathogen-driven cytokine networks and implications for applied microbiology

Mastitis is a common inflammatory disease in both humans and dairy animals, most frequently driven by bacterial pathogens such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Mycoplasma bovis (M. bovis), and Streptococcus uberis (S. uberis). These microbes deploy distinct virulence strategies yet share the ability to reshape T-cell-mediated immunity, thereby influencing infection outcomes, tissue damage, and chronicity. In this review, we summarize current evidence on how CD4⁺, CD8⁺, γδ T-cells, Tregs, and other T-cell subsets participate in mastitis-associated immune responses. We focus on pathogen-specific mechanisms, including S. aureus superantigen-induced immune deviation, M. bovis-driven prostaglandin E₂-STAT3-PD-L1 signalling and T-cell exhaustion, early CD8⁺ recruitment and cytokine imbalance in E. coli mastitis, and γδ T-cell activation during S. uberis infection. We further compare common and divergent strategies of immune evasion and dysregulated T-cell-mediated inflammation across these pathogens. Finally, we discuss how T-cell signatures and cytokine networks may inform the development of diagnostic biomarkers, immunomodulatory interventions, and vaccine candidates, with the potential to reduce antibiotic use and improve mastitis control in both human and veterinary settings.