Involvement of chemokine receptors and adhesion molecules in the regulation of Experimental Cerebral Malaria.

Abstract

Leukocytes in particular CD8+ T cells migration to the brain and parasite sequestration are involved in experimental cerebral malaria (ECM). We hypothesized that ECM is initiated by parasite sequestration in the brain, by adhering to endothelium and/or monocytes or macrophages. Firstly, we assessed the role of two chemokine receptors CCR2 and CCR5, in leukocyte trafficking to the brain and other organs in ECM and sequestration of infected red blood cells (iRBC). We infected CCR2-deficient mice (50% monocyte reduction) with PbAluc and treated with anti-M-CSF receptor mAb. CCR2-/- treated mice died of ECM with the same parasitemia and parasite biomass as non-treated mice. Next, we investigated the role of CCR5 in ECM. CCR5-deficient mice were as susceptible to ECM as WT mice with no difference in parasitemia and parasite accumulation. Lastly, we investigated the involvement of adhesion molecules (ICAM-1) in iRBC sequestration. Rag2-deficient and C57BL/6J mice treated with anti-ICAM-1 mAb showed an increase in parasitemia with no difference in bioluminescence imaging compared to non-treated mice. These results suggest that iRBC do not adhere to monocytes and/or macrophages; CCR5 is not involved in T cells recruitment; and ICAM-1 might not be the major determinant adhesion molecule during effector phase.