111 research outputs found
Recommended from our members
A mucosal vaccine against Chlamydia trachomatis generates two waves of protective memory T cells
Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ producing CD4 T-cells. By contrast, mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory T-cells that exacerbated subsequent Ct infection. We show that mucosal immunization with UV-Ct complexed with charge-switching synthetic adjuvant particles (cSAP) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b+CD103− dendritic cells (DCs), whereas UV-Ct accumulated in tolerogenic CD11b−CD103+ DCs. Regardless of vaccination route, UV-Ct-cSAP induced systemic memory T-cells, but only mucosal vaccination induced effector T-cells that rapidly seeded uterine mucosa with resident memory T-cells (TRM). Optimal Ct clearance required both TRM seeding and subsequent infection-induced recruitment of circulating memory T-cells. Thus, UV-Ct-cSAP vaccination generated two synergistic memory T-cell subsets with distinct migratory properties
Compensatory T Cell Responses in IRG-Deficient Mice Prevent Sustained Chlamydia trachomatis Infections
The obligate intracellular pathogen Chlamydia trachomatis is the most common cause of bacterial sexually transmitted diseases in the United States. In women C. trachomatis can establish persistent genital infections that lead to pelvic inflammatory disease and sterility. In contrast to natural infections in humans, experimentally induced infections with C. trachomatis in mice are rapidly cleared. The cytokine interferon-γ (IFNγ) plays a critical role in the clearance of C. trachomatis infections in mice. Because IFNγ induces an antimicrobial defense system in mice but not in humans that is composed of a large family of Immunity Related GTPases (IRGs), we questioned whether mice deficient in IRG immunity would develop persistent infections with C. trachomatis as observed in human patients. We found that IRG-deficient Irgm1/m3(-/-) mice transiently develop high bacterial burden post intrauterine infection, but subsequently clear the infection more efficiently than wildtype mice. We show that the delayed but highly effective clearance of intrauterine C. trachomatis infections in Irgm1/m3(-/-) mice is dependent on an exacerbated CD4+ T cell response. These findings indicate that the absence of the predominant murine innate effector mechanism restricting C. trachomatis growth inside epithelial cells results in a compensatory adaptive immune response, which is at least in part driven by CD4+ T cells and prevents the establishment of a persistent infection in mice
- …