Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract

Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune re...

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Main Authors: Jennifer D. Helble, Rodrigo J. Gonzalez, Ulrich H. von Andrian, Michael N. Starnbach
Format: Article
Language:English
Published: American Society for Microbiology 2020-03-01
Series:mBio
Subjects:
Online Access:https://doi.org/10.1128/mBio.00191-20
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spelling doaj-734392fc505d4901856e114927620e512021-07-02T05:19:37ZengAmerican Society for MicrobiologymBio2150-75112020-03-01112e00191-2010.1128/mBio.00191-20Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital TractJennifer D. HelbleRodrigo J. GonzalezUlrich H. von AndrianMichael N. StarnbachChlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ−/−, and IFN-γR−/− NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing C. trachomatis infection.https://doi.org/10.1128/mBio.00191-20chlamydiaifn-γt cellsgenital tract immunityinterferonsmucosal immunitymucosal pathogens
collection DOAJ
language English
format Article
sources DOAJ
author Jennifer D. Helble
Rodrigo J. Gonzalez
Ulrich H. von Andrian
Michael N. Starnbach
spellingShingle Jennifer D. Helble
Rodrigo J. Gonzalez
Ulrich H. von Andrian
Michael N. Starnbach
Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract
mBio
chlamydia
ifn-γ
t cells
genital tract immunity
interferons
mucosal immunity
mucosal pathogens
author_facet Jennifer D. Helble
Rodrigo J. Gonzalez
Ulrich H. von Andrian
Michael N. Starnbach
author_sort Jennifer D. Helble
title Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract
title_short Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract
title_full Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract
title_fullStr Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract
title_full_unstemmed Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract
title_sort gamma interferon is required for chlamydia clearance but is dispensable for t cell homing to the genital tract
publisher American Society for Microbiology
series mBio
issn 2150-7511
publishDate 2020-03-01
description Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ−/−, and IFN-γR−/− NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing C. trachomatis infection.
topic chlamydia
ifn-γ
t cells
genital tract immunity
interferons
mucosal immunity
mucosal pathogens
url https://doi.org/10.1128/mBio.00191-20
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