Description:
<jats:title>Abstract</jats:title>
<jats:p>Babesia microti is the primary etiologic agent of human babesiosis, an emerging infectious disease in the US. In healthy individuals, babesiosis typically causes a mild flu-like illness or is asymptomatic. In immunocompromised patients, particularly those with B cell lymphoma and treated with rituximab, babesiosis is severe, persistent, and sometimes fatal. The mechanisms by which the host controls this obligate parasite of erythrocytes are poorly understood. In C57Bl/6 mice, parasitemia is marginal and transient. Lack of mature B cells due to igh6 deficiency does not hinder resistance. In rag1-/- mice, however, parasitemia is intense and persists for at least three months. This pattern also is observed in athymic (nude) mice, in mice lacking TCRαβ cells and in MHCii-/- mice. Surprisingly, parasitemia is intense but transient in cd4-/- mice. In the spleens of these mice, CD8+ T cells and CD4-CD8- T cells greatly expand during the course of infection. Parasitemia resolves in cd4-/- cd8-/- mice, but persists in cd4-/- igh6-/- mice. Likewise, parasitemia persists in cd4-/- mice depleted of B cells by repeated administration of anti-CD20. Resolution of parasitemia in cd4-/- mice is concomitant with the rise in circulating Babesia specific IgG, but does not require Fc receptors as demonstrated in cd4-/- fcegr1-/- mice. Our studies establish that, in the absence of CD4, B cells are critical for resolution of babesiosis. The role of complement and cytokines will be discussed.</jats:p>