Interleukin-12 production is required for chlamydial antigen-pulsed dendritic cells to induce protection against live Chlamydia trachomatis infection

Immunization with dendritic cells pulsed ex vivo with antigens has been suc cessfully used to elicit primary antigen-specific immune responses. We repo rt that mouse bone marrow-derived dendritic cells pulsed with inactivated c hlamydial organisms induced strong protection against live chlamydial infec tion in a mouse lung infection model. Either the dendritic cells or chlamyd ial organisms alone or macrophages similarly pulsed with chlamydial organis ms failed to induce any significant protection. These observations suggest that dendritic cells can efficiently process and present chlamydial antigen s to naive T cells in vivo. Mice immunized with the chlamydia-pulsed dendri tic cells preferentially developed a Th1 cell-dominant response while mice immunized with the other immunogens did not, suggesting a correlation betwe en a Th1 cell-dominant response and protection against chlamydial infection . We further found that dendritic cells produced a large amount of interleu kin 12 (IL-12) upon ex vivo pulsing with inactivated chlamydial organisms, which may allow the dendritic cells to direct a Th1 cell-dominant response. Dendritic cells from mice deficient in the IL-12 p40 gene failed to produc e IL-12 after a similar ex vivo pulse with chlamydial organisms, and more i mportantly, immunization with these dendritic cells failed to induce a Th1 cell-dominant response and did not induce strong protection against chlamyd ial infection. Thus, the ability of dendritic cells to efficiently process and present chlamydial antigens and to produce IL-12 upon chlamydial-organi sm stimulation are both required for the induction of protection against ch lamydial infection. This information may be useful for the further design o f effective chlamydial vaccines.