Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>

<p>Abstract</p> <p>Background</p> <p>Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated.</p> <p>Methods</p> <p>Neutralization a...

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Main Authors: Peng Bo, Lu Chunxue, Tang Lingli, Yeh I-Tien, He Zhimin, Wu Yimou, Zhong Guangming
Format: Article
Language:English
Published: BMC 2011-12-01
Series:BMC Infectious Diseases
Subjects:
Online Access:http://www.biomedcentral.com/1471-2334/11/347
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author Peng Bo
Lu Chunxue
Tang Lingli
Yeh I-Tien
He Zhimin
Wu Yimou
Zhong Guangming
author_facet Peng Bo
Lu Chunxue
Tang Lingli
Yeh I-Tien
He Zhimin
Wu Yimou
Zhong Guangming
author_sort Peng Bo
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated.</p> <p>Methods</p> <p>Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with <it>C. muridarum </it>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.</p> <p>Results</p> <p>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 <it>C. muridarum </it>infection. However, the antibody blocking significantly enhanced <it>C. muridarum</it>-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues.</p> <p>Conclusions</p> <p>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 <it>C. trachomatis </it>organisms.</p>
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spelling doaj.art-337d1e55dc8a4d34ac191c4ed7c748142022-12-22T01:19:06ZengBMCBMC Infectious Diseases1471-23342011-12-0111134710.1186/1471-2334-11-347Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>Peng BoLu ChunxueTang LingliYeh I-TienHe ZhiminWu YimouZhong Guangming<p>Abstract</p> <p>Background</p> <p>Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated.</p> <p>Methods</p> <p>Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with <it>C. muridarum </it>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.</p> <p>Results</p> <p>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 <it>C. muridarum </it>infection. However, the antibody blocking significantly enhanced <it>C. muridarum</it>-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues.</p> <p>Conclusions</p> <p>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 <it>C. trachomatis </it>organisms.</p>http://www.biomedcentral.com/1471-2334/11/347<it>Chlamydia muridarum</it>Oviduct pathologyTim-3 &PD-L1 signaling pathways
spellingShingle Peng Bo
Lu Chunxue
Tang Lingli
Yeh I-Tien
He Zhimin
Wu Yimou
Zhong Guangming
Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>
BMC Infectious Diseases
<it>Chlamydia muridarum</it>
Oviduct pathology
Tim-3 &
PD-L1 signaling pathways
title Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>
title_full Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>
title_fullStr Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>
title_full_unstemmed Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>
title_short Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with <it>Chlamydia muridarum</it>
title_sort enhanced upper genital tract pathologies by blocking tim 3 and pd l1 signaling pathways in mice intravaginally infected with it chlamydia muridarum it
topic <it>Chlamydia muridarum</it>
Oviduct pathology
Tim-3 &
PD-L1 signaling pathways
url http://www.biomedcentral.com/1471-2334/11/347
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