Elimination of <i>Babesia microti</i> Is Dependent on Intraerythrocytic Killing and CD4+ T Cells

Abstract

Babesiosis is a tick-borne zoonosis caused by protozoans of the genus <i>Babesia</i>, apicomplexan parasites that replicate within erythrocytes. However, unlike related <i>Plasmodium</i> species, the pathogenesis of <i>Babesia</i> infection remains poorly understood. The primary etiological agent of babesiosis in the United States is <i>B. microti.</i> In healthy individuals, tick-transmitted infection with <i>Babesia</i> causes no specific clinical manifestations, with many having no symptoms at all. However, even in asymptomatic people, a <i>Babesia</i> carriage state can be established that can last up to a year or more. Current blood bank screening methods do not identify infected donors, and <i>Babesia</i> parasites survive blood-banking procedures and storage. Thus, <i>Babesia</i> can also be transmitted by infected blood, and it is currently the number one cause of reportable transfusion-transmitted infection in the United States. Despite a significant impact on human health, <i>B. microti</i> remains understudied. In this study, we evaluated the course of <i>Babesia</i> infection in three strains of mice, C57BL/6J, BALB/cJ, and C3H-HeJ, and examined the contribution of multiple immune parameters, including TLRs, B cells, CD4⁺ cells, IFN-γ, and NO, on the level of parasitemia and parasite clearance during acute babesiosis. We found that <i>B. microti</i> reaches high parasitemia levels during the first week of infection in all three mice strains before resolving spontaneously. Our results indicate that resolution of babesiosis requires CD4 T cells and a novel mechanism of parasite killing within infected erythrocytes.