Circulating Monocytes, Tissue Macrophages, and Malaria

Abstract

Malaria is a significant cause of global morbidity and mortality. The Plasmodium parasite has a complex life cycle with mosquito, liver, and blood stages. The blood stages can preferentially affect organs such as the brain and placenta. In each of these stages and organs, the parasite will encounter monocytes and tissue-specific macrophages-key cell types in the innate immune response. Interactions between the Plasmodium parasite and monocytes/macrophages lead to several changes at both cellular and molecular levels, such as cytokine release and receptor expression. In this review, we summarize current knowledge on the relationship between malaria and blood intervillous monocytes and tissue-specific macrophages of the liver (Kupffer cells), central nervous system (microglia), and placenta (maternal intervillous monocytes and fetal Hofbauer cells). We describe their potential roles in modulating outcomes from infection and areas for future investigation.

Figure 1

(a) Normal placenta. The dashed lines outline placental villi. Maternal RBCs are seen in the intervillous space. The placental villous (outlined with red dotted lines) is lined by the syncytiotrophoblast (STB). Fetal Hofbauer cells (HBCs) are located in the villous core. (b) Malaria-infected placenta. iRBCs (arrows) accumulate in the intervillous space, and the villous surface is denuded (arrowhead). Infected red blood cells (arrows) and maternal intervillous monocytes (MIM) are found within the intervillous space. A syncytial knot (SK) is a histologic sign of placental remodeling from pathologic processes. HBC: Hofbauer cell; STB: syncytiotrophoblast; MIM: maternal intervillous monocyte; SK: syncytial knot. Placental biopsies were stained with CD68, a monocyte/macrophage marker, and counterstained with hematoxylin.