The deletion of yeaJ gene facilitates Escherichia coli escape from immune recognition
Mammary gland-derived Escherichia coli ( E. coli ) is an important pathogen causing dairy cow mastitis. Mammary gland mucosal immunity against infectious E. coli mainly depends on recognition of pathogen-associated molecular patterns by innate receptors. Stimulator of interferon (IFN) gene (STING) has recently been the dominant mediator in reacting to bacterial intrusion and preventing inflammatory disorders. In this study, we firstly proved that diguanylate cyclase YeaJ relieves mouse mammary gland pathological damage by changing E. coli phenotypic and host STING-dependent innate immunity response. YeaJ decreases mammary gland circular vacuoles, bleeding and degeneration in mice. In addition, YeaJ participates in STING-IRF3 signaling to regulate inflammation in vivo . While in vitro , YeaJ decreases damage to macrophages (RAW264.7) but not to mouse mammary epithelial cells (EpH4-Ev). Consistent with the results in mouse mammary gland, yeaJ significantly activates STING/TBK1/IRF3 pathway in RAW264.7 as well. In conclusion, the deletion of yeaJ gene facilitates E. coli NJ17 escape from STING-dependent innate immunity recognition in vitro and in vivo . This study highlights a novel role for YeaJ in E. coli infection, which provides a better understanding of host-bacteria interactions and potential prophylactic strategies for infections. IMPORTANCE E. coli is the etiological agent of environmental mastitis in dairy cows, which cause massive financial losses worldwide. However, the pathophysiological role of yeaJ in the interaction between E. coli and host remains unclear. We found that YeaJ significantly influences various biological characteristics and suppresses severe inflammatory response as well as greater damage. YeaJ alleviates damage to macrophages (RAW264.7) and mouse mammary gland. Moreover, these effects of YeaJ are achieved at least partial by mediating the STING-IRF3 signaling pathway. In conclusion, the deletion of yeaJ gene facilitates E. coli NJ17 escape from STING-dependent innate immunity recognition in vitro and in vivo. This study is the basis for further research to better understand host-bacteria interactions and provides potential prophylactic strategies for infections.