Babesia bovis-stimulated macrophages express interleukin-1 beta, interleukin-12 tumor necrosis factor alpha, and nitric oxide and inhibit parasite replication in vitro

The tick-transmitted hemoparasite Babesia bovis causes an acute infection t hat results in persistence and immunity against challenge infection in catt le that control the initial parasitemia. Resolution of acute infection with this protozoal pathogen is believed to be dependent on products of activat ed macrophages (M phi), including inflammatory cytokines and nitric oxide ( NO) and its derivatives. B. bovis stimulates inducible nitric oxide synthas e (iNOS) and production of NO in bovine M phi, and chemical donors of NO in hibit the growth of B. bovis in vitro. However, the induction of inflammato ry cytokines in M phi by babesial parasites has not been described, and the antiparasitic activity of NO produced by B. bovis-stimulated M phi has not been definitively demonstrated. We report that monocyte-derived M phi acti vated by B. bovis expressed enhanced levels of inflammatory cytokines inter leukin-1 beta (IL-1 beta), IL-12, and tumor necrosis factor alpha that are important for stimulating innate and acquired immunity against protozoal pa thogens. Furthermore, a lipid fraction of B. bovis-infected erythrocytes st imulated iNOS expression and NO production by M phi. Cocultures of M phi an d B. bovis-infected erythrocytes either in contact or physically separated resulted in reduced parasite viability. However, NO produced by bovine M ph i in response to B. bovis-infected erythrocytes was only partially responsi ble for parasite growth inhibition, suggesting that additional factors cont ribute to the inhibition of B. bovis replication. These findings demonstrat e that B. bovis induces an innate immune response that is capable of contro lling parasite replication and that could potentially result in host surviv al and parasite persistence.