title: Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with Chlamydia muridarum.
abstract: BACKGROUND
  Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated.
  
  
  METHODS
  Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with C. muridarum organisms, mice with or without the dual antibody treatment were compared for live chlamydial organism shedding from the lower genital tract and inflammatory pathology in the upper genital tract.
  
  
  RESULTS
  Mice treated with anti-Tim-3 and anti-PD-L1 antibodies displayed a time course of live organism shedding similar to that of mice treated with equivalent amounts of isotype-matched IgG molecules. The combined antibody blocking failed to alter either the lower genital tract cytokine or systemic humoral and cellular adaptive responses to C. muridarum infection. However, the antibody blocking significantly enhanced C. muridarum-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues.
  
  
  CONCLUSIONS
  The Tim-3 and PD-L1-mediated signaling can significantly reduce pathologies in the upper genital tract without suppressing immunity against chlamydial infection, suggesting that Tim-3 and PD-L1-mediated negative regulation may be manipulated to attenuate tubal pathologies in women persistently infected with C. trachomatis organisms.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Peng
authors.forename: Chunxue
authors.initials: C
authors.lastname: Lu
authors.forename: Lingli
authors.initials: L
authors.lastname: Tang
authors.forename: I-Tien
authors.initials: IT
authors.lastname: Yeh
authors.forename: Zhimin
authors.initials: Z
authors.lastname: He
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors / Q000276:immunology*; D057138:Bacterial Shedding; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D005836:Genitalia, Female / Q000382:microbiology / Q000473:pathology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D051379:Mice; D008807:Mice, Inbred BALB C; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000276:immunology*; D060737:Reproductive Tract Infections / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; C442241:Havcr2 protein, mouse; D000072597:Hepatitis A Virus Cellular Receptor 2; D011991:Receptors, Virus