Macrophages Are the Determinant of Resistance to and Outcome of Nonlethal Babesia microti Infection in Mice

Abstract

cIn 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 times during the course 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 naive mice resulted in a slight reduction in parasitemia with improved survival compared to that of 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-␥) and tumor necrosis factor alpha (TNF-␣). Furthermore, depletion of macrophages at different times exaggerated the pathogenesis of the infection in deficient IFN-␥ ؊/؊ and severe combined immunodeficiency (SCID) mice. Collectively, our data provide important clues about the role of macrophages in the resistance and control of B. microti and imply that the severity of the infection in immunocompromised patients might be due to impairment of macrophage function.

Elimination of Babesia microti Is Dependent on Intraerythrocytic Killing and CD4+ T Cells

“…Instead intra-erythrocyte parasite death was associated with elevated levels of the anti-inflammatory cytokines IL-10, and G-CSF. Other studies of B. microti infection, like the current study, noted serum IL-10 production but also reported modest elevation of serum pro-inflammatory cytokines including IFN-γ (33, 34), which we did not observe. IL-12p40 was also elevated; this cytokine can form homodimers that may play an antagonistic role in the development of IL-12p70 responses, though this remains unclear.…”

The pathology of the spleen in lethal canine babesiosis caused by Babesia rossi

“…The spleen does however play a very important role in the clearance of haemoprotozoal organisms as evidenced by the death of splenectomized rats infected with Plasmodium berghei . Another study, similar in methodology, showed the importance of macrophages during the control of both the acute and resolving infections of Babesia microti in mice . In particular, the specific absence of marginal zone and RP macrophages contributed to the failure to control the parasitaemia in the infected mice …”

Babesiosis

“…2, 27-28, 30 Most fatal cases of human babesiosis occur in splenectomized individuals, although asplenia does not always result in death or even severe illness. The spleen plays a critical role in protection against Babesia spp.…”