Inhibition of a live-attenuated chlamydia oral vaccine in the large intestine is dependent on CD11c-expressing cells that produce IL-23.

The live-attenuated oral vaccine intrOv is an IFNγ-susceptible mutant of C. muridarum that is rapidly cleared from the large intestine by IFNγ-producing group 3 innate lymphoid cells (IFNγ+ILC3s), while the wild-type C. muridarum maintains long-lasting colonization. Although we have previously shown that IL-23 receptor signaling is essential for IFNγ+ILC3s to clear intrOv, the cellular source of IL-23 remains unknown. In the current study, we found that intrOv induces IL-23 in the large intestine, which correlates with intrOv inhibition. Mice deficient in IL-23p19 fail to inhibit intrOv, demonstrating the necessity for IL-23 to promote the inhibition of intrOv. To identify the responsible IL-23 producers, transgenic mice expressing CD11c promoter-driven diphtherial toxin receptor are used to deplete dendritic cells. We found that depletion of CD11c-expressing cells significantly reduces IL-23 and IFNγ, allowing intrOv to grow, while wild-type CD11c-expressing cells are sufficient to rescue IL-23p19-deficient mice to inhibit intrOv in the large intestine. Thus, we have demonstrated that CD11c-expressing cells inhibit the live-attenuated chlamydia oral vaccine intrOv via an IL-23-dependent mechanism, providing novel information to improve the safety and efficacy of intrOv and to reveal the intricate interactions of an obligate intracellular bacterium with host mucosal tissues.