TLR2 Signaling Pathway Combats Streptococcus uberis Infection by Inducing Mitochondrial Reactive Oxygen Species Production.

Bin Li,Jinfeng Miao,Xiangan Han,Zhixin Wan,Vanhnaseng Phouthapane,Jiakun Zuo,Yuanyuan Xu,Zhenglei Wang

doi:10.3390/cells9020494

Abstract

Mastitis caused by Streptococcus uberis (S. uberis) is a common and difficult-to-cure clinical disease in dairy cows. In this study, the role of Toll-like receptors (TLRs) and TLR-mediated signaling pathways in mastitis caused by S. uberis was investigated using mouse models and mammary epithelial cells (MECs). We used S. uberis to infect mammary glands of wild type, TLR2−/− and TLR4−/− mice and quantified the adaptor molecules in TLR signaling pathways, proinflammatory cytokines, tissue damage, and bacterial count. When compared with TLR4 deficiency, TLR2 deficiency induced more severe pathological changes through myeloid differentiation primary response 88 (MyD88)-mediated signaling pathways during S. uberis infection. In MECs, TLR2 detected S. uberis infection and induced mitochondrial reactive oxygen species (mROS) to assist host in controlling the secretion of inflammatory factors and the elimination of intracellular S. uberis. Our results demonstrated that TLR2-mediated mROS has a significant effect on S. uberis-induced host defense responses in mammary glands as well as in MECs.

Highlights

Mastitis is an inflammation caused by intra-mammary infection, leading to losses in the dairy industry [1]
We explored the roles of TLR2 and TLR4 in S. uberis infections in TLR2−/− and TLR4−/− mice to further understand the molecular defense mechanism in S. uberis mastitis
No histological changes were observed in wild-type C57BL/6 (WT-B6) or WT-B10 mammary glands of control mice, whereas, there was some suspicion of tissue damage in TLR2−/− and TLR4−/− control mice (Figure 1A)

Summary

Introduction

Mastitis is an inflammation caused by intra-mammary infection, leading to losses in the dairy industry [1]. Streptococcus uberis (S. uberis) is an environmental pathogen emerging as the most important mastitis-causing agent in some regions [2]. Previous studies in our laboratory have demonstrated that persistent inflammation, including swelling, secretory epithelial cell degeneration, and polymorphonuclear neutrophilic leukocyte (PMN) infiltration, occurs in mammary tissue following injection with S. uberis [4]. This inflammatory responce caused by S. uberis is lighter than that of caused by E. coli [4]. These pathological responses are connected with S. uberis intracellular infection as it escapes the elimination of immune cells and induces persistent infection

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