Project Title

Estrogen receptors affect Chlamydia muridarum infection in mice

Authors' Affiliations

Amy Berry, Department of Biomedical Sciences and the Center of Excellence for Inflammation, Infectious Disease, and Immunity at Quillen College of Medicine, East Tennessee State University, Johnson City, TN Jennifer Kintner, Department of Biomedical Sciences at Quillen College of Medicine, East Tennessee State University, Johnson City, TN Jennifer V Hall, Department of Biomedical Sciences and the Center of Excellence for Inflammation, Infectious Disease, and Immunity at Quillen College of Medicine, East Tennessee State University, Johnson City, TN

Location

BEECH MTN. ROOM 120

Start Date

4-12-2019 9:40 AM

End Date

4-12-2019 9:55 AM

Faculty Sponsor’s Department

Biomedical Sciences

Name of Project's Faculty Sponsor

Dr. Jennifer Hall

Type

Oral Presentation

Classification of First Author

Graduate Student-Doctoral

Project's Category

Microbiology

Abstract Text

Chlamydia trachomatis is a leading cause of bacterial genital infection in the US and worldwide. The chlamydial replication cycle is biphasic, meaning it enters the host cell as an infectious elementary body (EB), differentiates into an actively dividing reticulate body (RB) inside of a vacuole-like compartment, called a chlamydial inclusion, and differentiates back into EB form before exiting the host. Studies have demonstrated that estrogen aids Chlamydia infection in human and swine endometrial cells and in guinea pigs. Our prior data showed that antibody blockage of estrogen receptors or exposure to the ERβ antagonist tamoxifen in vitro decreased the development of chlamydial inclusions. Given these observations, we wanted to further examine the role of ER signaling on chlamydial infection in a murine model. We hypothesized that the absence of estrogen receptors would alter the establishment and/or progression of chlamydial infection in mice. To test this hypothesis, we compared C. muridarum infection in wild type (ERαWT or ERβWT) versus knockout (ERαKO or ERβKO) mice. Groups of eight ERαWT, ERβWT, ERαKO, or ERβKO mice were Depo-Provera treated seven days prior to vaginal infection with C. muridarum. Vaginal swabs were taken every three days for 21 days to monitor infection by EB titer analysis. Interestingly, titer data showed that peak EB shedding occurred earlier in the ERαKO mice compared to the ERαWT. At day 3 pi, EB shedding from ERαKO mice was 12-fold greater than shedding from ERαWT mice. On day 6, however, ERαWT mice shed >3-fold more EB than ERαKO mice. Conversely, there was no significant difference observed in ERβKO versus ERβWT mice or in ERαKO versus ERβKO mice. In a subset of experiments, genital tracts were collected on day 9pi and processed for flow cytometry analysis of the immune response to infection. ERαKO mice had significantly more monocytes and macrophages than ERαWT and ERβKO mice, as well as significantly more T cells than ERβKO mice. There was no significant difference in the immune cells in ERβKO and ERβWT mice. Together, these data suggest that: 1) the absence of ERs in mice does not inhibit chlamydial infection as has been observed in human cells in vitro; and 2) C. muridarum infection progression is affected by ERα signaling, possibly via alterations in the immune response.

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Apr 12th, 9:40 AM Apr 12th, 9:55 AM

Estrogen receptors affect Chlamydia muridarum infection in mice

BEECH MTN. ROOM 120

Chlamydia trachomatis is a leading cause of bacterial genital infection in the US and worldwide. The chlamydial replication cycle is biphasic, meaning it enters the host cell as an infectious elementary body (EB), differentiates into an actively dividing reticulate body (RB) inside of a vacuole-like compartment, called a chlamydial inclusion, and differentiates back into EB form before exiting the host. Studies have demonstrated that estrogen aids Chlamydia infection in human and swine endometrial cells and in guinea pigs. Our prior data showed that antibody blockage of estrogen receptors or exposure to the ERβ antagonist tamoxifen in vitro decreased the development of chlamydial inclusions. Given these observations, we wanted to further examine the role of ER signaling on chlamydial infection in a murine model. We hypothesized that the absence of estrogen receptors would alter the establishment and/or progression of chlamydial infection in mice. To test this hypothesis, we compared C. muridarum infection in wild type (ERαWT or ERβWT) versus knockout (ERαKO or ERβKO) mice. Groups of eight ERαWT, ERβWT, ERαKO, or ERβKO mice were Depo-Provera treated seven days prior to vaginal infection with C. muridarum. Vaginal swabs were taken every three days for 21 days to monitor infection by EB titer analysis. Interestingly, titer data showed that peak EB shedding occurred earlier in the ERαKO mice compared to the ERαWT. At day 3 pi, EB shedding from ERαKO mice was 12-fold greater than shedding from ERαWT mice. On day 6, however, ERαWT mice shed >3-fold more EB than ERαKO mice. Conversely, there was no significant difference observed in ERβKO versus ERβWT mice or in ERαKO versus ERβKO mice. In a subset of experiments, genital tracts were collected on day 9pi and processed for flow cytometry analysis of the immune response to infection. ERαKO mice had significantly more monocytes and macrophages than ERαWT and ERβKO mice, as well as significantly more T cells than ERβKO mice. There was no significant difference in the immune cells in ERβKO and ERβWT mice. Together, these data suggest that: 1) the absence of ERs in mice does not inhibit chlamydial infection as has been observed in human cells in vitro; and 2) C. muridarum infection progression is affected by ERα signaling, possibly via alterations in the immune response.