CD4 T cell-dependent IFNγ production and antibody are the two best known effectors for protective immunity against Chlamydia female reproductive tract (FRT) infection. Nevertheless, mice lacking either IFNγ 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 IFNγ and B cells play complementary roles in host defense against Chlamydia and evaluated their relative contributions in systemic and mucosal tissues. Using mice deficient in both IFNγ and B cells (IFNγ-/- x μMT), we showed that mice lacking both effectors were highly susceptible to lethal systemic bacterial dissemination following Chlamydia muridarum intravaginal infection. Passive transfer of immune convalescent serum, but not recombinant IFNγ, reduced bacterial burden in both systemic and mucosal tissues in IFNγ-/- x μMT mice. Notably, over the course of primary infection, we observed a reduction of bacterial shedding of more than 2 orders of magnitude in IFNγ-/- x μMT mice following both C. muridarum and C. trachomatis FRT infections. In contrast, no protective immunity against C. muridarum reinfection was detected in the absence of IFNγ and B cells. Together, our results suggest that IFNγ and B cells synergize to combat systemic Chlamydia dissemination, while additional IFNγ and B cell-independent mechanisms exist for host resistance to Chlamydia in the lower FRT.
Keywords: Chlamydia; IFNγ; antibody; dissemination; infection; reinfection.