Characterization of TLR2, NOD2, and related cytokines in mammary glands infected by Staphylococcus aureus in a rat model

BACKGROUND Staphylococcus aureus causes subclinical mastitis as well as persistent and chronic infections in cattle. Bovine mastitis induced by S. aureus is often refractory to antibiotic treatment. Local innate immune defenses play an important role in eliminating the invading bacteria. TLR2 and NOD2 are important pathogen recognition receptors, but their functions have not been investigated in the context of early stages of mastitis. The present study examined TLR2, NOD2, and related cytokines in mammary glands infection induced by S. aureus at early stages in a rat mastitis model. FINDINGS All inoculated mammary glands developed mastitis. Acute changes were induced in mammary tissues infected with S. aureus at early stages and then chronic infections persisted until the end of the experiment. TLR2 and NOD2 mRNA expression increased significantly after inoculation with S. aureus. The expression levels of cytokine mRNAs, including TNF-α, IL-1β, IL-6, IL-10, and CXCL1, also increased. TGF-β1 expression was suppressed at early phase and IFN-γ mRNA expression increased significantly at a later stage. CONCLUSIONS Mammary innate immune responses were activated after S. aureus inoculation. TLR2, NOD2, and inflammatory cytokines (TNF-α, IL-1β, IL-6, CXCL1, IL-10, TGF-β1, and IFN-γ) are involved in the response to mastitis induced by S. aureus.