CCR5 contributes to adverse outcomes during malaria in pregnancy.

Abstract

CCR5 is a chemokine receptor that mediates cell recruitment to sites of inflammation. It has been previously reported that the expression of CCR5 is increased in the placentas of women with malaria, a disease characterized by causing deliveries with low birth weight among other complications. CCR5 has been associated with pathology of protozoan infections during pregnancy but its role during malaria in pregnancy has not been elucidated. In the present work, we assessed the pregnancy outcome, placental structure, and levels of inflammatory markers of pregnant C57BL/6 and CCR5-/- mice infected or not with Plasmodium berghei NK65, with the purpose of determine the role of CCR5 in pregnancy associated malaria complications. We demonstrated that the expression of CCR5 mRNA increases in late pregnancy placentas of C57BL/6 when compared to uninfected controls. Infected pregnant C57BL/6 mice showed preterm birth, decreased fetal weight, placental inefficiency, and reduced placental vascular space. On the other hand, CCR5 deficiency led to increased levels of maternal parasitemia, reduced fetal weight and placental inefficiency compared to C57BL/6 mice. However, the infection did not cause additional changes in these parameters or in the incidence of preterm delivery in infected CCR5-/- mice in relation to C57BL/6 mice, showing that CCR5 may contribute to the adverse effects caused by infection during pregnancy. This improvement in pregnancy outcome, observed in infected CCR5-/- mice, was accompanied by lower placental levels of the inflammatory markers, such as TNF and NAG. Furthermore, it was observed that the placentas of CCR5-/- animals showed structural differences in relation to C57BL/6 mice, which could improve the efficiency of maternal-fetal exchanges, reflecting on fetal weight. Taken together, these results indicate that CCR5 expression contributes to the adverse outcomes caused by malaria in late pregnancy.