A Mechanism For The Induction Of Type 2 Immune Responses By Protease Antigen In The Genital Tract

Abstract

The genital mucosa is a barrier constantly exposed to variety of pathogens, allergens, and external stimuli. Although both allergen exposure and parasites infection are not rarely occurred in the genital area, a mechanism of immune responses, especially type 2 immunity in the genital mucosa has rarely been studied. Here, we show Th2 induction in the genital mucosa in response to a model antigen, protease papain. Intravaginal papain immunization induced type 2 immunity in a manner dependent on protease activity and the estrous phase of mice. In addition, IL-33 was released into the vaginal mucosa after intravaginal papain immunization, leading to activation of type 2 innate lymphoid cells (ILC2s). Moreover, the IL-33-MyD88 signaling pathway was critical for the induction of type 2 immunity. We also found that Th2 differentiation in response to intravaginal papain requires a specific DC subset, which is controlled by IRF4. These findings suggest that type 2 immunity is induced by a unique mechanism in the genital tract, which is an important, but often overlooked, barrier surface.