The complement receptor CRIg dominates clearance of intravascular parasites during African trypanosome infection

Abstract

Abstract Kupffer cells (KCs), the liver resident macrophages, play a prominent role in clearance of blood-borne pathogens. The mechanisms by which KCs engulf circulating parasites such as African trypanosomes have yet to be determined. Here we show that depletion of KCs resulted in uncontrolled parasitemia in mice infected with Trypanosoma congolense, indicating the essential role of KCs in clearance of intravascular parasites. By using intravital microscopy, we further investigated the dynamics of interactions of KCs with circulating T. congolense in real-time. The results demonstrate that KCs catch circulating parasites in the presence of specific IgM and IgG antibodies, but fail to do so in the absence of specific antibodies. Complement C3 is critically involved in the capture of the parasites mediated by both IgM and IgG. We further demonstrate that complement receptor CRIg, but not CR3, is crucial for KCs to catch the parasites. In support of the findings gained by in vivo imaging, mice deficient of C3 or CRIg, but not CR3, could not control the first wave of parasitemia, and had a dramatic reduced survival time compared to wild-type mice following infection with T. congolense (10 days vs over 100 days). Collectively, our data demonstrate that CRIg play a dominant role in the clearance of circulating parasites by KCs in an antibody dependent manner.