IFNγ and antibody synergize to enhance protective immunity againstChlamydiadissemination and female reproductive tract reinfections

Abstract 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 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 IFNγ 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 IFNγ and B cells (IFNγ -/- x µMT), we showed that mice lacking both effectors are highly susceptible to lethal systemic Chlamydia dissemination. Passive transfer of immune convalescent serum, but not recombinant IFNγ, reduced bacterial burden in both systemic and mucosal tissues in IFNγ -/- x µMT mice. Moreover, we observed a reduction of bacterial shedding of more than two orders of magnitude in IFNγ -/- x µMT mice following both Chlamydia muridarum and Chlamydia trachomatis infections. Lastly, protective immunity against C. muridarum reinfection was completely abrogated in the absence of IFNγ and B cells. Our results suggest that IFNγ and B cells synergize to combat bacterial dissemination, while an IFNγ and B cell-independent mechanism exists for host resistance to Chlamydia in the FRT.