title: Toll-like Receptors 4 and 5 Cooperatively Initiate the Innate Immune Responses to Uropathogenic Escherichia coli Infection in Mouse Epididymal Epithelial Cells.
abstract: Uropathogenic Escherichia coli (UPEC) may cause epididymitis and impair male fertility. The mechanisms underlying the innate immune responses to UPEC infection in the epididymis are not fully understood. This study showed that UPEC induced innate immune responses in mouse epididymal epithelial cells (EECs) through the activation of Toll-like receptor 4 (TLR4) and TLR5. Infection with UPEC significantly induced the expression of proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 6, and monocyte chemoattractant protein 1, in EECs through the activation of nuclear factor kappa B. Moreover, UPEC induced the production of type 1 interferons by EECs through the activation of interferon regulatory factor 3. The UPEC-induced innate immune responses were significantly reduced in the EECs of Tlr4 or Tlr5 knockout mice. The innate immune responses were further reduced in Tlr4 and Tlr5 double-knockout EECs. Furthermore, we demonstrated that TLR4 and TLR5 cooperatively initiated the epididymal innate immune responses to UPEC infection in vivo. The results provide novel insights into the mechanisms underlying the epididymal innate immune responses to UPEC infection.
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Cheng
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Basic Medicine, Peking Union Medical College; Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China dshan@ibms.pumc.edu.cn.
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004822:Epididymis / Q000378:metabolism* / Q000382:microbiology; D007113:Immunity, Innate / Q000502:physiology*; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000378:metabolism*; D056689:Uropathogenic Escherichia coli / Q000276:immunology*
chemical_list: D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5
keywords: Toll-like receptor; UPEC; epididymis; innate immune response