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Macrophage is the determinant of resistance to and outcome of non-lethal Babesia microti infection in mice.

[severe combined immunodeficiency]

In the present study, we examined the contributions of macrophages to the outcome of infection with Babesia microti, the etiological agent of human and rodent babesiosis, in BALB/c mice. Mice were treated with clodronate liposome at different time courses of B. microti infection in order to deplete the macrophages. Notably, a depletion of host macrophages at the early and acute phases of infection caused a significant elevation of parasitemia associated with remarkable mortality in the mice. The depletion of macrophages at the resolving and latent phases of infection resulted in an immediate and temporal exacerbation of parasitemia coupled with mortality in mice. Reconstituting clodronate liposome-treated mice at the acute phase of infection with macrophages from naïve mice resulted in a slight reduction in parasitemia with improved survival, as compared to mice that received the drug alone. These results indicate that macrophages play a crucial role in the control of and resistance to B. microti infection in mice. Moreover, analyses of host immune responses revealed that macrophage-depleted mice diminished their production of Th1 cell-cytokines, including gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Furthermore, depletion of macrophage at different time courses exaggerated the pathogenesis of the infection in deficient IFN-γ(-)/(-) and severe combined immunodeficiency (SCID) mice. Collectively, our data provides important clues about the role of macrophages in the resistance and control of B. microti and implies that the severity of the infection in immunocompromised patients might be due to impairment of the macrophages' function.

Diseases presenting "acute phases" symptom

  • severe combined immunodeficiency

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