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theses

Chlamydia is the most common cause of sexually transmitted bacterial infection worldwide and it leads to severe complications for women who become infected. Following initial infection, the bacterial pathogen ascends from the lower genital tract to the upper genital tract leading to pelvic inflammation and scarring of inflamed tissue. The scarring can lead to ductal obstruction, causing retention of fluid in the upper genital tract and ovaries, termed hydrosalpinx. This inflammation due to Chlamydia infection can lead to infertility. Despite the commonality of the disease and its severe consequences, the molecular pathogenesis and mechanism of pelvic inflammation following Chlamydia infection has yet to be elucidated. We investigated the molecular pathogenesis and its relation to host autophagy here. The ATG5 gene is required for autophagy. Our lab has previously shown via mouse model that deletion of the ATG5 gene in myeloid cells results in a significant increase in upper genital tract inflammation following Chlamydia infection. To further investigate the role of autophagy in Chlamydia pathogenesis, mice with deleted ATG5 gene in epithelial cells were intravaginally infected with Chlamydia. The infection was monitored through weekly vaginal swabbing and calculation of Chlamydia bacterial titers from each swab. After Chlamydia infection cleared, the animals were sacrificed, upper genital tract pathology was observed and cytokine analysis was conducted on the vaginal swabs that were taken throughout the infection. The p62 autophagy protein acts as a scaffold to bring bacterial pathogen to autophagy machinery. In the current study, p62-deficient mice were obtained and infected with Chlamydia. Vaginal swabbing throughout Chlamydia infection allowed us to estimate bacterial titers and assay the host cytokine response to the infection, and finally the upper genital tracts of the animals were removed for observation. We found no significant difference in the pathology, bacterial clearance, or cytokine analysis between epithelial Atg5-deficient animals and wild type animals. This suggests that the Chlamydia bacteria may be employing mechanisms to evade or inhibit host autophagy in epithelial cells to promote its own survival. Additionally, there was no significant difference in the pathology, bacterial clearance, or cytokine analysis between the p62-deficient animals and wild type animals.

ETD_4889

M.A.

Includes bibliographical references

by Lauren Battaglia

doi:10.7282/T3ZK5DPG

ETD graduate

The author owns the copyright to this work.