Ccr7 is critical for resistance against experimental Trypanosoma cruzi infection (56.4)

Abstract

Abstract The protozoan parasite Trypanosoma cruzi is the etiological agent of Chagas’ Disease, which affects ~12 million people in Latin America despite coordinated international control efforts. Cardiomyopathy due to chronic inflammation and fibrosis is the most common and serious presentation of Chagas’ Disease, but its pathogenesis is poorly understood. Several inflammatory chemokines and chemokine receptors have been implicated in mouse models of T. cruzi infection; however, roles for homeostatic chemokines have not previously been reported. Here, we found that mRNA for the homeostatic chemokine Ccl19 and its receptor Ccr7 were both increased in the heart during the acute phase after infection of WT C57BL/6 mice. Consistent with an important functional role, infection was uniformly fatal during the acute phase in infected Ccr7-/- mice, whereas mortality was only 10% in WT control mice. Death in infected KO mice was associated with uncontrolled parasitemia and increased parasite burden in both heart and liver, whereas infected WT mice controlled parasite burden in all 3 compartments. Leukocyte infiltration was also greater in the hearts of infected KO mice compared to infected WT controls, and was characterized by a lower frequency of CD8+ T cells and a greater frequency of Gr-1hiCD11b+IA- cells. Thus Ccr7 is a critical factor for survival and control of T. cruzi infection in C57BL/6 mice. The mechanisms of resistance conferred by Ccr7 are currently under investigation.