Staphylococcus aureus induces mammary gland fibrosis through activating the TLR/NF-κB and TLR/AP-1 signaling pathways in mice.

To investigate the TLR-NF-κB/AP-1 pathways in S. aureus infection-induced mammary gland fibrosis, mice were infected with S. aureus isolated from the mammary glands of cows with mastitis. Lactating mice were divided into three groups: control group (CON); PBS control group (PBS) and the S. aureus-treated group (S. aureus). Pathological observations revealed that neutrophil infiltration into mammary gland tissue was obviously induced by S. aureus at the early stage of infection (1-7 d). With persistent S. aureus infection, mammary gland fibrosis developed and was characterized by infiltration and proliferation of macrophage, lymphocyte and fibroblast and ECM hyperplasia (7-21 d). Immunohistochemistry staining showed upregulation of fibrosis associated cytokines viz bFGF and PDGF-BB. Real-time qPCR and Western blot analysis revealed that transcription and translation of TLR2, TLR4, bFGF, PDGF-BB, α-SMA and COL Ⅰ α1 was significantly upregulated by S. aureus. NF-κB p65 and AP-I c-jun were translocated into the nucleus after S. aureus infection. There was no remarkable difference between the CON and PBS groups. The datas indicate that mammary gland fibrosis in mice is induced by S. aureus, which promotes cytokine release and the expression of ECM though activating the TLR/NF-κB p65 and TLR/AP-1 c-jun signaling pathways.