Fig. 1.

A hypothetical model of action of chemokines in human severe malaria syndromes. (A) After binding to the brain microvasculature, sequestered pRBC induce activation of vascular endothelial cells, which results in the release of inflammatory cytokines as well as CXCR3 and CCR5 binding chemokines. It is possible that local production of these chemokines stimulates the accumulation of CXCR3⁺ and CCR5⁺ leucocytes. In addition, some CXCR3 chemokines such as CXCL10 that have angiostatic activity could inhibit endothelial cell regeneration of the brain microvasculature, thereby compromising the integrity of the blood–brain barrier. (B) In the placenta, both maternal and fetal cells might contribute to the production of β-chemokines in response to infection. These mediators stimulate the recruitment of monocytes and macrophages to the intravillous space, which appears to be associated with adverse pregnancy outcomes.