Phagocytosis, Interferon-γ, IL-21, and CD4+ MHC class II-restricted T cells in resistance to Babesia microti infection (43.14)

Abstract

Abstract Babesiosis is an emerging infectious disease caused by the hematoprotozoan parasite Babesia microti. The mechanisms of resistance to B. microti are not fully understood. The laboratory has developed a murine model of babesiosis with many of the features of the human disease that is used to examine the genetic determinants of resistance. The goal of the present study was to identify cellular processes that convey resistance to this parasitic infection. We established that the depletion of macrophages by chronic administration of clodronate liposomes resulted in early (0 to 30 days post-infection) hyperacute phase parasitemia (quantified as percent parasitized erythrocytes) but did not affect late phase (days 35-50) clearance of B. microti. In contrast, the absence of MHC-ii or the αβ T cell receptor prevents both early and late resistance. We find that early resistance requires the production of the cytokine IL-21. We also observed that the dual loss of CD4 and IL-21 results in the complete loss of resistance. We therefore hypothesize that IL-21 activates CD4+ T lymphocytes to synthesize IFN- γ that, in turn, activates macrophages to phagocytose and destroy B. microti infected red blood cells or B. microti itself. A model of resistance that incorporates these observations will be presented.