Chlamydia muridarum induces pathology in the female upper genital tract via distinct mechanisms

Heze Yu, Hui Lin, Lingxiang Xie, Lingli Tang, Jianlin Chen, Zhiguang Zhou, Jiangdong Ni, Guangming Zhong

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice and is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed CD4+ T cell-mediated protective immunity and a CD8+ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8+ T cells were evaluated, we found, surprisingly, that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice and suggesting a pathogenic mechanism that is independent of CD8+ T cells. We further found that depletion of CD4+ T cells from CD8+ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4+ T cells became pathogenic in mice genetically deficient in CD8+ T cells. Since depletion of CD4+ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8+ T cell-deficient mice, we propose that in the absence of CD8+ T cells, some CD4+ T cells may remain protective (as in C57BL/6J mice), while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms, depending upon host genetics and infection conditions. The CD8+ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4+ T cells promote chlamydial pathogenicity.

Original languageEnglish (US)
Article numbere00145
JournalInfection and Immunity
Volume87
Issue number8
DOIs
StatePublished - Jan 1 2019

Fingerprint

Chlamydia muridarum
Pathology
T-Lymphocytes
Virulence
Inbred C57BL Mouse
Chlamydia trachomatis
Infection
Chlamydia Infections

Keywords

  • CD4/CD8 T cells
  • Chlamydia
  • Hydrosalpinx

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Chlamydia muridarum induces pathology in the female upper genital tract via distinct mechanisms. / Yu, Heze; Lin, Hui; Xie, Lingxiang; Tang, Lingli; Chen, Jianlin; Zhou, Zhiguang; Ni, Jiangdong; Zhong, Guangming.

In: Infection and Immunity, Vol. 87, No. 8, e00145, 01.01.2019.

Research output: Contribution to journalArticle

Yu, Heze ; Lin, Hui ; Xie, Lingxiang ; Tang, Lingli ; Chen, Jianlin ; Zhou, Zhiguang ; Ni, Jiangdong ; Zhong, Guangming. / Chlamydia muridarum induces pathology in the female upper genital tract via distinct mechanisms. In: Infection and Immunity. 2019 ; Vol. 87, No. 8.
@article{932f85100403495ba2d584bff6d87925,
title = "Chlamydia muridarum induces pathology in the female upper genital tract via distinct mechanisms",
abstract = "Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice and is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed CD4+ T cell-mediated protective immunity and a CD8+ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8+ T cells were evaluated, we found, surprisingly, that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice and suggesting a pathogenic mechanism that is independent of CD8+ T cells. We further found that depletion of CD4+ T cells from CD8+ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4+ T cells became pathogenic in mice genetically deficient in CD8+ T cells. Since depletion of CD4+ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8+ T cell-deficient mice, we propose that in the absence of CD8+ T cells, some CD4+ T cells may remain protective (as in C57BL/6J mice), while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms, depending upon host genetics and infection conditions. The CD8+ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4+ T cells promote chlamydial pathogenicity.",
keywords = "CD4/CD8 T cells, Chlamydia, Hydrosalpinx",
author = "Heze Yu and Hui Lin and Lingxiang Xie and Lingli Tang and Jianlin Chen and Zhiguang Zhou and Jiangdong Ni and Guangming Zhong",
year = "2019",
month = "1",
day = "1",
doi = "10.1128/IAI.00145-19",
language = "English (US)",
volume = "87",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - Chlamydia muridarum induces pathology in the female upper genital tract via distinct mechanisms

AU - Yu, Heze

AU - Lin, Hui

AU - Xie, Lingxiang

AU - Tang, Lingli

AU - Chen, Jianlin

AU - Zhou, Zhiguang

AU - Ni, Jiangdong

AU - Zhong, Guangming

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice and is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed CD4+ T cell-mediated protective immunity and a CD8+ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8+ T cells were evaluated, we found, surprisingly, that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice and suggesting a pathogenic mechanism that is independent of CD8+ T cells. We further found that depletion of CD4+ T cells from CD8+ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4+ T cells became pathogenic in mice genetically deficient in CD8+ T cells. Since depletion of CD4+ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8+ T cell-deficient mice, we propose that in the absence of CD8+ T cells, some CD4+ T cells may remain protective (as in C57BL/6J mice), while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms, depending upon host genetics and infection conditions. The CD8+ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4+ T cells promote chlamydial pathogenicity.

AB - Sexually transmitted infection with Chlamydia trachomatis may lead to fibrotic blockage in women's upper genital tracts, resulting in tubal infertility. Intravaginal inoculation with C. muridarum readily induces fibrotic blockage or hydrosalpinx in mice and is used for investigating C. trachomatis pathogenicity. Using this model in combination with an antibody depletion approach, we confirmed CD4+ T cell-mediated protective immunity and a CD8+ T cell-dependent pathogenic mechanism during chlamydial infection in C57BL/6J mice. However, when mice genetically deficient in CD8+ T cells were evaluated, we found, surprisingly, that these mice were still able to develop robust hydrosalpinx following C. muridarum infection, both contradicting the observation made in C57BL/6J mice and suggesting a pathogenic mechanism that is independent of CD8+ T cells. We further found that depletion of CD4+ T cells from CD8+ T cell-deficient mice significantly reduced chlamydial induction of hydrosalpinx, indicating that CD4+ T cells became pathogenic in mice genetically deficient in CD8+ T cells. Since depletion of CD4+ T cells both promoted chlamydial infection and reduced chlamydial pathogenicity in CD8+ T cell-deficient mice, we propose that in the absence of CD8+ T cells, some CD4+ T cells may remain protective (as in C57BL/6J mice), while others may directly contribute to chlamydial pathogenicity. Thus, chlamydial pathogenicity can be mediated by distinct host mechanisms, depending upon host genetics and infection conditions. The CD8+ T cell-deficient mouse model may be useful for further investigating the mechanisms by which CD4+ T cells promote chlamydial pathogenicity.

KW - CD4/CD8 T cells

KW - Chlamydia

KW - Hydrosalpinx

UR - http://www.scopus.com/inward/record.url?scp=85070421842&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070421842&partnerID=8YFLogxK

U2 - 10.1128/IAI.00145-19

DO - 10.1128/IAI.00145-19

M3 - Article

C2 - 31085708

AN - SCOPUS:85070421842

VL - 87

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 8

M1 - e00145

ER -