CD14+ monocytes are the main leucocytic sources of CXCL10 in response to Plasmodium falciparum

The CXCR3 chemokine CXCL10 or IFN-gamma inducible protein 10 (IP-10) has been identified as an important biomarker of cerebral malaria (CM) mortality in children. Studies in mouse malaria infection models have shown that CXCL10 blockade alleviates brain intravascular inflammation and protects infected mice from CM. Despite the key role that CXCL10 plays in the development of CM, the leucocytic sources of CXCL10 in response to human malaria are not known. Here we investigated CXCL10 responses to Plasmodium falciparum in peripheral blood mononuclear cells (PBMCs). We found that PBMCs from malaria-unexposed donors produce CXCL10 in response to P. falciparum and that this response is IFN-gamma-dependent. Moreover, CD14+ monocytes were identified as the main leucocytic sources of CXCL10 in peripheral blood, suggesting an important role for innate immune responses in the activation of this pathway involved in the development of symptomatic malaria.