Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with Chlamydia muridarum
1 Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
2 Department of Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
3 Cancer Research Institute, Xiangya School of Medicine, Central South University, 110 Xiangya Rd, Changsha, Hunan 410078, China
4 Department of Microbiology and Pathology, University of South China, 28 West Changsheng Rd, Hengyang, Hunan 421001, China
BMC Infectious Diseases 2011, 11:347 doi:10.1186/1471-2334-11-347Published: 14 December 2011
Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated.
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.
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.
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.