DISRUPTION OF CD40-CD40 LIGAND INTERACTIONS RESULTS IN AN ENHANCED SUSCEPTIBILITY TO LEISHMANIA-AMAZONENSIS INFECTION

To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L(-/- )) mice with Leishmania amazonensis. Although wild-type mice were susc eptible to infection and developed progressive ulcerative lesions, tis sue parasite burdens in CD40L(-/-) mice were significantly higher. Thi s heightened susceptibility to infection was associated with an impair ed T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFN gamma, lymphotoxin-tumor necrosis f actor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L(- /-) mice failed to generate a protective immune response after immuniz ation. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.