CD40, but not CD40L, is required for the optimal priming of T cells and control of aerosol M. tuberculosis infection.

CD40(-/-) mice succumbed to low-dose aerosol infection with M. tuberculosis due to deficient IL-12 production leading to impaired priming of IFN-gamma T cell responses. In contrast, CD40L(-/-) mice were resistant to M. tuberculosis. This asymmetry in outcome of infection between the two knockout strains is likely due to the existence of an alternative ligand for CD40. Both in vitro M. tuberculosis infection and recombinant M. tuberculosis Hsp70 elicited IL-12 production from WT dendritic cells. This response was absent in both CD40(-/-) dendritic cells and CD40(-/-) mice, suggesting that M. tuberculosis Hsp70 serves as an alternative ligand for CD40 in vivo.