Cargando…

The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo

Genital Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial infection is influenced by various factors, including the female sex hormones estrogen and progesterone. Sex hormone levels n...

Descripción completa

Detalles Bibliográficos
Autores principales: Gravitte, Amy, Kintner, Jennifer, Brown, Stacy, Cobble, Allison, Kennard, Benjamin, Hall, Jennifer V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831676/
https://www.ncbi.nlm.nih.gov/pubmed/36636722
http://dx.doi.org/10.3389/fcimb.2022.939944
_version_ 1784867895521574912
author Gravitte, Amy
Kintner, Jennifer
Brown, Stacy
Cobble, Allison
Kennard, Benjamin
Hall, Jennifer V.
author_facet Gravitte, Amy
Kintner, Jennifer
Brown, Stacy
Cobble, Allison
Kennard, Benjamin
Hall, Jennifer V.
author_sort Gravitte, Amy
collection PubMed
description Genital Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial infection is influenced by various factors, including the female sex hormones estrogen and progesterone. Sex hormone levels naturally fluctuate in women throughout their menstrual cycle. Varying concentrations of estrogen and progesterone may impact the progression of chlamydial infection and the host’s immune response to Chlamydia. Estrogen signals through estrogen receptors (ERs), ERα and ERβ. These receptors are similar in structure and function, but are differentially expressed in tissues throughout the body, including the genital tract and on cells of the immune system. In this study, we used ovariectomized (OVT) BALB/c mice to investigate the impact of long-term administration of physiologically relevant concentrations of estrogen (E2), progesterone (P4), or a combination of E2/P4 on the progression of and immune response to C. muridarum infection. Additionally, we used ERα and ERβ knockout C57/BL6 mice to determine the how ERs affect chlamydial infection and the resulting immune response. Estrogen exposure prevented C. muridarum infection in vaginally infected OVT mice exposed to E2 alone or in combination with P4, while OVT or Sham mice exposed to hormone free, P4 or depo-medroxyprogesterone acetate shed similar amounts of chlamydiae. The hormonal environment also altered T cell recruitment and IFNϵ production the genital tracts of infected OVT and Sham mice on day 10 post infection. The absence of ERα, but not ERβ, in ER knockout mouse strains significantly changed the timing of C. muridarum infection. ERαKO mice shed significantly more chlamydiae at day 3 post infection and resolved the infection faster than WT or ERβKO animals. At day 9 post infection, flow cytometry showed that ERαKO mice had more T cells present and targeted RNA sequencing revealed increased expression of CD4 and FOXP3, suggesting that ERαKO mice had increased numbers of regulatory T cells compared to ERβKO and WT mice. Mock and chlamydia-infected ERαKO mice also expressed more IFNϵ early during infection. Overall, the data from these studies indicate that sex hormones and their receptors, particularly ERα and ERβ, differentially affect C. muridarum infection in murine models of infection.
format Online
Article
Text
id pubmed-9831676
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-98316762023-01-11 The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo Gravitte, Amy Kintner, Jennifer Brown, Stacy Cobble, Allison Kennard, Benjamin Hall, Jennifer V. Front Cell Infect Microbiol Cellular and Infection Microbiology Genital Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial infection is influenced by various factors, including the female sex hormones estrogen and progesterone. Sex hormone levels naturally fluctuate in women throughout their menstrual cycle. Varying concentrations of estrogen and progesterone may impact the progression of chlamydial infection and the host’s immune response to Chlamydia. Estrogen signals through estrogen receptors (ERs), ERα and ERβ. These receptors are similar in structure and function, but are differentially expressed in tissues throughout the body, including the genital tract and on cells of the immune system. In this study, we used ovariectomized (OVT) BALB/c mice to investigate the impact of long-term administration of physiologically relevant concentrations of estrogen (E2), progesterone (P4), or a combination of E2/P4 on the progression of and immune response to C. muridarum infection. Additionally, we used ERα and ERβ knockout C57/BL6 mice to determine the how ERs affect chlamydial infection and the resulting immune response. Estrogen exposure prevented C. muridarum infection in vaginally infected OVT mice exposed to E2 alone or in combination with P4, while OVT or Sham mice exposed to hormone free, P4 or depo-medroxyprogesterone acetate shed similar amounts of chlamydiae. The hormonal environment also altered T cell recruitment and IFNϵ production the genital tracts of infected OVT and Sham mice on day 10 post infection. The absence of ERα, but not ERβ, in ER knockout mouse strains significantly changed the timing of C. muridarum infection. ERαKO mice shed significantly more chlamydiae at day 3 post infection and resolved the infection faster than WT or ERβKO animals. At day 9 post infection, flow cytometry showed that ERαKO mice had more T cells present and targeted RNA sequencing revealed increased expression of CD4 and FOXP3, suggesting that ERαKO mice had increased numbers of regulatory T cells compared to ERβKO and WT mice. Mock and chlamydia-infected ERαKO mice also expressed more IFNϵ early during infection. Overall, the data from these studies indicate that sex hormones and their receptors, particularly ERα and ERβ, differentially affect C. muridarum infection in murine models of infection. Frontiers Media S.A. 2022-12-27 /pmc/articles/PMC9831676/ /pubmed/36636722 http://dx.doi.org/10.3389/fcimb.2022.939944 Text en Copyright © 2022 Gravitte, Kintner, Brown, Cobble, Kennard and Hall https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Gravitte, Amy
Kintner, Jennifer
Brown, Stacy
Cobble, Allison
Kennard, Benjamin
Hall, Jennifer V.
The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo
title The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo
title_full The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo
title_fullStr The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo
title_full_unstemmed The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo
title_short The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo
title_sort hormonal environment and estrogen receptor signaling alters chlamydia muridarum infection in vivo
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831676/
https://www.ncbi.nlm.nih.gov/pubmed/36636722
http://dx.doi.org/10.3389/fcimb.2022.939944
work_keys_str_mv AT gravitteamy thehormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT kintnerjennifer thehormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT brownstacy thehormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT cobbleallison thehormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT kennardbenjamin thehormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT halljenniferv thehormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT gravitteamy hormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT kintnerjennifer hormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT brownstacy hormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT cobbleallison hormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT kennardbenjamin hormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo
AT halljenniferv hormonalenvironmentandestrogenreceptorsignalingalterschlamydiamuridaruminfectioninvivo