Antigen-specific CD4 T cell-derived gamma interferon is both necessary and sufficient for clearing chlamydia from the small intestine but not the large intestine

Hui Lin, Conghui He, John J. Koprivsek, Jianlin Chen, Zhiguang Zhou, Bernard Arulanandam, Zhenming Xu, Lingli Tang, Guangming Zhong

Research output: Contribution to journalArticle

Abstract

The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in 4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in / T cells or CD4 T cells but not CD8 T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 T cells in clearing Chlamydia from the small intestine. The CD4 T cell-dependent clearance is likely mediated by gamma interferon (IFN-), since mice deficient in IFN- but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN- was sufficient for clearing Chlamydia from the small intestine but not the large intestine. Mice deficient in developing Chlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-producing CD4 but not CD8 T cells from immunized donor mice were sufficient for eliminating Chlamydia from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing Chlamydia from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.

Original languageEnglish (US)
Article numbere00055-19
JournalInfection and Immunity
Volume87
Issue number6
DOIs
StatePublished - Jan 1 2019

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CD4 Antigens
Chlamydia
Large Intestine
Interferon-gamma
Small Intestine
T-Lymphocytes
Interferons
Gastrointestinal Tract
Immunity
Chlamydia muridarum
Chlamydia trachomatis
Infection

Keywords

  • Chlamydia
  • Gamma interferon
  • Genital tract immunity
  • Small intestine immunity
  • Th1 immunity

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Antigen-specific CD4 T cell-derived gamma interferon is both necessary and sufficient for clearing chlamydia from the small intestine but not the large intestine. / Lin, Hui; He, Conghui; Koprivsek, John J.; Chen, Jianlin; Zhou, Zhiguang; Arulanandam, Bernard; Xu, Zhenming; Tang, Lingli; Zhong, Guangming.

In: Infection and Immunity, Vol. 87, No. 6, e00055-19, 01.01.2019.

Research output: Contribution to journalArticle

Lin, Hui ; He, Conghui ; Koprivsek, John J. ; Chen, Jianlin ; Zhou, Zhiguang ; Arulanandam, Bernard ; Xu, Zhenming ; Tang, Lingli ; Zhong, Guangming. / Antigen-specific CD4 T cell-derived gamma interferon is both necessary and sufficient for clearing chlamydia from the small intestine but not the large intestine. In: Infection and Immunity. 2019 ; Vol. 87, No. 6.
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abstract = "The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in 4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in / T cells or CD4 T cells but not CD8 T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 T cells in clearing Chlamydia from the small intestine. The CD4 T cell-dependent clearance is likely mediated by gamma interferon (IFN-), since mice deficient in IFN- but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN- was sufficient for clearing Chlamydia from the small intestine but not the large intestine. Mice deficient in developing Chlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-producing CD4 but not CD8 T cells from immunized donor mice were sufficient for eliminating Chlamydia from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing Chlamydia from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.",
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AU - Lin, Hui

AU - He, Conghui

AU - Koprivsek, John J.

AU - Chen, Jianlin

AU - Zhou, Zhiguang

AU - Arulanandam, Bernard

AU - Xu, Zhenming

AU - Tang, Lingli

AU - Zhong, Guangming

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N2 - The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in 4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in / T cells or CD4 T cells but not CD8 T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 T cells in clearing Chlamydia from the small intestine. The CD4 T cell-dependent clearance is likely mediated by gamma interferon (IFN-), since mice deficient in IFN- but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN- was sufficient for clearing Chlamydia from the small intestine but not the large intestine. Mice deficient in developing Chlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-producing CD4 but not CD8 T cells from immunized donor mice were sufficient for eliminating Chlamydia from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing Chlamydia from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.

AB - The genital tract pathogen Chlamydia trachomatis is frequently detected in the gastrointestinal tract, but the host immunity that regulates chlamydial colonization in the gut remains unclear. In a Chlamydia muridarum-C57 mouse model, chlamydial organisms are cleared from the genital tract in 4 weeks, but the genital organisms can spread to the gastrointestinal tract. We found that the gastrointestinal chlamydial organisms were cleared from the small intestine by day 28, paralleling their infection course in the genital tract, but persisted in the large intestine for long periods. Mice deficient in / T cells or CD4 T cells but not CD8 T cells showed chlamydial persistence in the small intestine, indicating a critical role for CD4 T cells in clearing Chlamydia from the small intestine. The CD4 T cell-dependent clearance is likely mediated by gamma interferon (IFN-), since mice deficient in IFN- but not interleukin 22 (IL-22) signaling pathways rescued chlamydial colonization in the small intestine. Furthermore, exogenous IFN- was sufficient for clearing Chlamydia from the small intestine but not the large intestine. Mice deficient in developing Chlamydia-specific Th1 immunity showed chlamydial persistence in the small intestine. Finally, IFN-producing CD4 but not CD8 T cells from immunized donor mice were sufficient for eliminating Chlamydia from the small intestine but not the large intestine of recipient mice. Thus, we have demonstrated a critical role for Th1 immunity in clearing Chlamydia from the small intestine but not the large intestine, indicating that chlamydial colonization in different regions of the gastrointestinal tract is regulated by distinct immune mechanisms.

KW - Chlamydia

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KW - Genital tract immunity

KW - Small intestine immunity

KW - Th1 immunity

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