title: Roles of Toll-like receptors 2 and 4 in mediating experimental autoimmune orchitis induction in mice.
abstract: The mammalian testis is an immunoprivileged site where male germ cell antigens are immunologically tolerated under physiological conditions. However, some pathological conditions can disrupt the immunoprivileged status and induce autoimmune orchitis, an etiological factor of male infertility. Mechanisms underlying autoimmune orchitis induction are largely unknown. The present study investigated the roles of Toll-like receptor 2 (TLR2) and TLR4 in mediating the induction of experimental autoimmune orchitis (EAO) in mice after immunization with male germ cell antigens emulsified with complete Freund adjuvant. Wild-type mice developed severe EAO after three immunizations, which was characterized by leukocyte infiltration, autoantibody production, and impaired spermatogenesis. Tlr2 or Tlr4 deficient mice showed relatively low susceptibility to EAO induction compared with wild-type mice. Notably, Tlr2 and Tlr4 double knockout mice were almost completely protected from EAO induction. Moreover, we demonstrated that TLR2 was crucial in mediating autoantibody production in response to immunization. The results imply that TLR2 and TLR4 cooperatively mediate EAO induction.
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Zhenghui
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Shutao
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: Center for Biomedical Research, The Population Council, New York, New York.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Center for Biomedical Research, The Population Council, New York, New York.
authors.forename: C Yan
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: School of Biological Science, University of Hong Kong, Hong Kong, China.
authors.forename: Will M
authors.initials: WM
authors.lastname: Lee
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China dshan@ibms.pumc.edu.cn.
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D005854:Germ Cells / Q000276:immunology; D007114:Immunization; D007248:Infertility, Male / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009920:Orchitis / Q000150:complications / Q000276:immunology* / Q000503:physiopathology*; D013737:Testis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D001323:Autoantibodies; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D005620:Freund's Adjuvant
keywords: Toll-like receptor; autoimmune orchitis; testis