Macrophage Migration Inhibitory Factor Contributes to Adverse Outcomes of Experimental Gestational Malaria across Pregnancy Stages

Abstract

Malaria infection during pregnancy, particularly caused by Plasmodium falciparum, poses significant risks, such as maternal anemia, low birth weight, preterm delivery, and increased infant mortality. This study investigated the role of macrophage migration inhibitory factor (MIF) in modulating pregnancy outcomes in a mouse model of gestational malaria. Herein, Mif-deficient (Mif^–/–) and Mif-sufficient (wild-type) mice were used to evaluate the impact of MIF on maternal-fetal immune interactions during Plasmodium infection in three different stages of pregnancy. Mif^–/– mice exhibited lower embryo resorption rates, preserved decidualization, and improved spiral artery remodeling compared with wild-type counterparts. Notably, although Mif deficiency was associated with increased parasitemia levels in late gestation, a shift toward a more anti-inflammatory phenotype in the uteroplacental tissues of infected mice contributed to better pregnancy outcomes. These results highlight the complex interplay between immune regulation and pregnancy in the context of malaria, indicating that targeting Mif may offer a therapeutic strategy to mitigate adverse pregnancy effects in infected individuals.