INDUCTION OF PROTECTIVE IMMUNITY AGAINST THE RESPIRATORY CHLAMYDIA MURIDARUM CHALLENGE BY PER-ORAL IMMUNIZATION

Author

Aurore Rysha, Southern Illinois University CarbondaleFollow

Date of Award

12-1-2024

Degree Name

Master of Science

Department

Molecular Biology Microbiology and Biochemistry

First Advisor

Konjufca, Vjollca

Abstract

Pneumonia, a leading cause of global morbidity and mortality, is caused by various microorganisms, with Chlamydia pneumoniae (Cpn) accounting for 1% to 20% of community-acquired pneumonia (CAP) cases in adults. Currently, no vaccine for Chlamydia has been approved for human use. To induce immune responses at mucosal surfaces such as the lungs, mucosal immunization is necessary. Building on our earlier findings that per oral (PO) immunization induced immune responses in the female reproductive tract, we hypothesized that mucosal (PO) immunization through the gastrointestinal tract could also induce protective immunity in the lungs. We further hypothesized that the recruitment of monocytes via CCR2 signaling is important for this protection. In this study, using the mouse model of infection with Chlamydia muridarum (Cm) we tested the efficacy of per oral (PO) immunization in inducing protective immunity in the respiratory tract. The role of the chemokine receptor CCR2 in monocyte recruitment and in immune response following Cm challenge or PO immunization was investigated. We show that PO-SC immunized mice, both wild-type and CCR2-/- were protected from the respiratory Cm challenge showing significantly less weight loss, reduced lung inflammation and bacterial burden compared to unimmunized controls. PO-SC immunization was also the only immunization approach that resulted in the induction of Cm-specific SIgA antibodies in the bronchoalveolar lavage (BAL) along with higher serum IgG, indicating the induction of effective local and systemic immune responses. This study shows the potential of PO-SC immunization in priming the mucosal immune system, providing enhanced protection against Cm infection, and indicates that the organized lymphoid tissues of the gastrointestinal (GI) tract can regulate the immunity in the lungs. Importantly, we show that CCR2 signaling, while critical for protection in unimmunized mice, becomes dispensable after immunization. Additionally, we demonstrate that in CCR2-/- mice, the recruitment of Ly6C+ cells are reduced, emphasizing the role of CCR2 signaling in immune cell recruitment. These results show the importance of mucosal immunity in fighting against Cm and present a promising approach for vaccine development against Chlamydia spp.