Research Article: IFN?-producing iNKTs restrict a live-attenuated chlamydia oral vaccine in the large intestine
Abstract:
Chlamydia muridarum continuously sheds live organisms and persists in the large intestine following intracolonic inoculation, while the live-attenuated chlamydia oral vaccine intrOv, an IFN?-susceptible mutant of C. muridarum , fails to do so. IFN? delivered by group 3 innate lymphoid cells (ILC3s) have been shown to block intrOv shedding. We now report that mice deficient in lymphocytes but competent in ILCs allowed intrOv to persist, revealing a critical role of lymphocytes for preventing intrOv persistence. The responsible lymphocyte subsets are natural killer T cells (NKTs), as mice deficient in either CD1d or ?2m permitted intrOv to persist. We further narrowed the responsible cells to invariant NKTs (iNKTs) that produce IFN?, as mice deficient in TCR? J18 segment (Traj18), T-bet, or IFN? failed to prevent intrOv persistence. Consistently, intrOv induced IFN? + iNKTs, and wild-type iNKTs prevented intrOv persistence in mice deficient in either lymphocytes or IFN?. Thus, IFN? + iNKTs are both necessary and sufficient for preventing intrOv persistence, while IFN? + ILC3s are for blocking intrOv shedding, revealing a division of labor between IFN? + iNKTs and IFN? + ILC3s in regulating the interaction of the obligate intracellular Chlamydia with host mucosal tissue. The information is also essential for improving the safety and efficacy of intrOv as an oral vaccine.
Introduction:
Chlamydia comprises multiple species of obligate intracellular bacteria that colonize mucosal tissues of different host species, with Chlamydia trachomatis infecting human mucosal tissues in the genital tract (serovars D to K) and the eye (serovars A to C), leading to severe complications ( 1 – 3 ). The genital C. trachomatis serovars are also frequently detected in the human gastrointestinal (GI) tract ( 4 , 5 ). The mouse-adapted C. muridarum has been widely used to investigate the pathogenic mechanisms of C.…
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