Project Title

Estrogen treatment protects mice from C. muridarum infection

Authors' Affiliations

Amy Gravitte, Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN Jen Kintner, Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN Stacy Brown, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN Benjamin Kennard, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN Allison Cobble, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN Jennifer Hall, Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN

Faculty Sponsor’s Department

Biomedical Sciences

Type

Oral Competitive

Classification of First Author

Graduate Student-Doctoral

Project's Category

Microbiology

Abstract Text

Chlamydia is the most commonly reported sexually transmitted infection in the US, with an estimated 4 million new cases in 2018 alone. In addition to humans, Chlamydia infects other animals including mice, and mice have become a popular model for the study of Chlamydia infection. Female sex hormones (FSH) estrogen (E2) and progesterone (P4) rise and fall in a cyclic fashion in both humans and mice, and it is well established that these hormones affect the establishment and progression of genital chlamydial infection. Prior studies that used a co-culture model of human endometrial epithelial cells (IK cells) grown on extracellular matrix-coated inserts over human stromal cells (SHT cells) showed that E2 treatment enhanced initial chlamydial infection and production of progeny Chlamydia compared to hormone free (HF), P4 or combination E2’E2/P4 treatment. This led to the hypothesis that the treatment of ovariectomized (OVX) mice with E2 would enhance chlamydial infection compared to mice treated with no hormone, P4, or a combination of E2 and P4. We ordered OVX mice from Jackson Laboratories and surgically implanted silastic capsules that contained E2, P4, E2/P4, or no hormone diluted in sesame oil. A gas chromatography method was developed to test E2 and P4 concentration in mouse serum, ensuring that hormone levels were physiologically relevant. 8 days after the implantation of the capsules, mice were vaginally-inoculated with C. muridarum¸ a chlamydial species that mimics human chlamydial infection in mice. Every 3 days post infection (pi), for 21 days, we vaginally swabbed mice to determine how much C. muridarum each mouse shed and created a graphical representation of chlamydial shedding. A subset of mice were sacrificed on day 10pi so that presence and identity of immune cells could be analyzed by flow cytometry. Surprisingly, E2 alone and E2/P4 treatment completely protected mice from chlamydial infection. HF-treated mice peaked in chlamydial shedding on day 3pi, and P4-treated mice peaked on day 9pi. Flow cytometry data showed that E2-treated mice had a significantly reduced T cell presence in the genital tract. Thus far, our data suggest that FSH affect chlamydial infection in mice differently than in humans. This observation could have important implications for a field that is heavily reliant on murine studies.

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Estrogen treatment protects mice from C. muridarum infection

Chlamydia is the most commonly reported sexually transmitted infection in the US, with an estimated 4 million new cases in 2018 alone. In addition to humans, Chlamydia infects other animals including mice, and mice have become a popular model for the study of Chlamydia infection. Female sex hormones (FSH) estrogen (E2) and progesterone (P4) rise and fall in a cyclic fashion in both humans and mice, and it is well established that these hormones affect the establishment and progression of genital chlamydial infection. Prior studies that used a co-culture model of human endometrial epithelial cells (IK cells) grown on extracellular matrix-coated inserts over human stromal cells (SHT cells) showed that E2 treatment enhanced initial chlamydial infection and production of progeny Chlamydia compared to hormone free (HF), P4 or combination E2’E2/P4 treatment. This led to the hypothesis that the treatment of ovariectomized (OVX) mice with E2 would enhance chlamydial infection compared to mice treated with no hormone, P4, or a combination of E2 and P4. We ordered OVX mice from Jackson Laboratories and surgically implanted silastic capsules that contained E2, P4, E2/P4, or no hormone diluted in sesame oil. A gas chromatography method was developed to test E2 and P4 concentration in mouse serum, ensuring that hormone levels were physiologically relevant. 8 days after the implantation of the capsules, mice were vaginally-inoculated with C. muridarum¸ a chlamydial species that mimics human chlamydial infection in mice. Every 3 days post infection (pi), for 21 days, we vaginally swabbed mice to determine how much C. muridarum each mouse shed and created a graphical representation of chlamydial shedding. A subset of mice were sacrificed on day 10pi so that presence and identity of immune cells could be analyzed by flow cytometry. Surprisingly, E2 alone and E2/P4 treatment completely protected mice from chlamydial infection. HF-treated mice peaked in chlamydial shedding on day 3pi, and P4-treated mice peaked on day 9pi. Flow cytometry data showed that E2-treated mice had a significantly reduced T cell presence in the genital tract. Thus far, our data suggest that FSH affect chlamydial infection in mice differently than in humans. This observation could have important implications for a field that is heavily reliant on murine studies.

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