IFN gamma and Antibody Synergize To Enhance Protective Immunity against Chlamydia Dissemination and Female Reproductive Tract Reinfections

CD4 T cell-dependent IFN gamma production and antibody are the 2 best known effectors for protective immunity against Chlamydia female reproductive tract (FRT) infection. Nevertheless, mice lacking either IFN gamma or B cells can clear the vast majority of Chlamydia from the FRT, while suffering from varying degrees of disseminated infection. In this study, we investigated whether IFN gamma and B cells play complimentary roles in host defense against Chlamydia and evaluated their relative contributions in systemic and mucosal tissues. Using mice deficient in both IFN gamma and B cells (IFN gamma x AMT), we showed that mice lacking both effectors are highly susceptible to lethal systemic bacterial dissemination following Chlamydia muridarum intravaginal infection. Passive transfer of immune convalescent-phase serum, but not recombinant IFN gamma, reduced bacterial burden in both systemic and mucosal tissues in IFN gamma(-/-) x mu MT mice. Notably, over the course of primary infection, we observed a reduction of bacterial shedding of more than 2 orders of magnitude in IFN gamma(-/-) x mu MT mice following both C. muridarum and Chlamydia trachomatis FRT infections. In contrast, protective immunity against C muridarum reinfection was completely abrogated in the absence of IFN gamma and B cells. Together, our results suggest that IFN gamma and B cells synergize to combat systemic Chlamydia dissemination, while additional IFN gamma and B cell-independent mechanisms exist for host resistance to Chlamydia in the lower FRT.