A mixed Th1/Th2 response induces optimal resistance to Leishmania braziliensis (43.21)

Abstract

Abstract Leishmania braziliensis is a protozoan that causes cutaneous lesions that heal spontaneously or induces a disease where the parasites metastasize to the nasopharyngeal mucosa. The factors responsible for the severe forms of the disease remain poorly understood, but an exaggerated Th1 response is associated with the immunopathology observed in these patients. In the absence of IFN-γ or iNOS mice are extremely susceptible to L. braziliensis, indicating that Th1 responses are essential to control these parasites. However, we hypothesized that a more moderated response might be associated with less pathology. Since we previously found that CD8 T cells inhibit a Th2 response in leishmaniasis, we tested whether depletion of CD8 T cells might promote a mixed Th1/Th2 response and less pathology. In fact, BALB/c mice infected with L. braziliensis and depleted of CD8 T cells developed smaller lesions, and unexpectedly were better able to control the parasites. This enhanced protection was accompanied by an increase in IL-4 and IL-5 levels, and an infiltration of neutrophils and eosinophils into the lesions. Eosinophils were essential for the increased resistance, since the protective effect of anti-CD8 treatment was reversed when mice were depleted of eosinophils by anti-CCR3 or anti-IL-5 monoclonal antibodies. Taken together, these data demonstrate that a mixed Th1/Th2 response induces optimal control of a L. braziliensis infection, and eosinophils are required for this outcome.