SYSTEMIC AND MUCOSAL ANTIBODY RESPONSES IN MICE PER-ORALLY INFECTED AND VACCINATED WITH CHLAMYDIA MURIDARUM

Author

Sondus Kahil, Southern Illinois University CarbondaleFollow

Date of Award

5-1-2018

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Konjufca, Vjollca

Second Advisor

Fix, Douglas

Abstract

Chlamydia spp. is the most commonly sexually transmitted bacterial pathogen that infects epithelial cells of mucosal surfaces such as the conjunctiva, gastrointestinal (GI), respiratory, and genital tracts. Chlamydial infections of the reproductive tract can lead to damaging pathology such as severe inflammation, tissue scarring, and infertility. Although antimicrobial therapy such as treatment with azithromycin is effective against chlamydial genital infections, chlamydial infections of the GI tract however, are much more difficult to eradicate after the establishment of a persistent infection. The resolution of chlamydial infections requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Antibodies (abs), especially IgG1, play an important role in the resolution of chlamydial infections. Parenteral immunizations such as subcutaneous (SC) injections generally induce serum IgG1 antibodies which aid in the elimination of pathogens. However, to induce mucosal antibodies, immunization via mucosal routes such per-oral (PO) immunizations are necessary to clear infections at mucosal sites such as the GI tract. Since systemic immune responses from parenteral immunization often do not elicit a mucosal immune response, they are ineffective against mucosal pathogens such as Chlamydia spp. ii In this work we characterize the systemic and mucosal antibody responses to per-oral (PO) infections and subcutaneous (SC) immunizations with Chlamydia muridarum. We also examine prime-boost immunization strategies for inducing a robust systemic and mucosal antibody responses to C. muridarum. We show that a PO infection with C. muridarum induces serum IgG2c and IgM and as well induce secretion of IgA (sIgA) in the gut. We found that SC boosting of PO-infected mice results in a serum IgG1 response. Our results showed that priming (PO or SC) with C. muridarum followed by SC boosting results in serum IgG2c, IgM, and IgG1 antibodies as well as IgA secretion in the gut. We also show that PO infection with C. muridarum (PO or SC) and SC boosting inhibits the secretion of IgG1 in the gut. Findings from this work will be relevant for understanding Chlamydia spp. pathogenesis and designing more effective mucosal vaccines.