IFNγ 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 two best known effectors for protective immunity against Chlamydia female reproductive tract (FRT) infection. Nevertheless, mice lacking either IFN{gamma} or B cells are capable of clearing vast majority of Chlamydia from the female reproductive tract (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 {micro}MT), we showed that mice lacking both effectors are highly susceptible to lethal systemic Chlamydia dissemination. Passive transfer of immune convalescent serum, but not recombinant IFN{gamma}, reduced bacterial burden in both systemic and mucosal tissues in IFN{gamma}-/- x {micro}MT mice. Moreover, we observed a reduction of bacterial shedding of more than two orders of magnitude in IFN{gamma}-/- x {micro}MT mice following both Chlamydia muridarum and Chlamydia trachomatis infections. Lastly, protective immunity against C. muridarum reinfection was completely abrogated in the absence of IFN{gamma} and B cells. Our results suggest that IFN{gamma} and B cells synergize to combat bacterial dissemination, while an IFN{gamma} and B cell-independent mechanism exists for host resistance to Chlamydia in the FRT.