PI: Dr. Caroline Kijogi

Donor/Funder: EDCTP – European and Developing Countries Clinical Trials Partnership

Reference: TMA 2018 CDF – 2835

Duration: 2020-2023

Summary of the Project

Macrophages account for one of the most abundant leucocytes infiltrating the uterine lining during pregnancy. They play a key role in the maintenance of a healthy pregnancy by promoting implantation, trophoblast invasion, placentation, tissue remodelling and angiogenesis. Macrophages are present at all stages of pregnancy unlike other leukocytes and are integral in the immunological adaptations that facilitate tolerance of the semi-allogenic foetus. Due to their plasticity and heterogeneity they may act as either pro- or anti-inflammatory mediators.

The activation state and function of macrophages is dependent on the local tissue microenvironment (secreted cytokines, chemokines, growth factors, hormones as well as interactions with related cells), enabling their polarization into either of the two distinct subsets; the classically activated, M1 macrophages which are pro-inflammatory and the alternatively activated, M2 macrophages which are anti-inflammatory and immunoregulatory. During the course of pregnancy, an M1 bias is observed transiently at initial immunological phase then a switch to M2 phenotype ensues till parturition, which is an inflammatory event characterized by a predominant M1 phenotype.

Infections during pregnancy can disrupt the uterine microenvironment and have profound effects on macrophage activity and subsequently the pregnancy outcome. One such infection is the Plasmodium falciparum infection which causes massive recruitment of monocytes and macrophages to the intervillous space of the placenta, the site of sequestration of infected erythrocytes. We hypothesize that the accumulation of these cells causes an M1/M2 imbalance possibly with deleterious effects on the growing foetus. We shall therefore test this hypothesis by examining the expression of cell surface markers for M1 and M2 macrophages, assessing the localization of these placental macrophage subsets and testing their functional capacity in in vitro polarization studies.

Findings from this study will lead to a better understanding of P. falciparum mediated macrophage polarization during placental infection and could be probed further in the development immuno-therapeutic tools to improve outcomes during malaria in pregnancy.

This project is part of the EDCTP2 programme supported by the European Union