Inflammation-associated anemia and the role of monocyte-derived inflammatory hemophagocytes in a model of blood-stage malaria

Malaria is caused by protozoan parasites of the Plasmodium species and is a major health problem within malaria-endemic regions. Disease symptoms range from mild to severe, and severe malaria is associated with a variety of complications, including severe malarial anemia. Malarial anemia can be life-threatening, especially in the most vulnerable groups – young children and pregnant women. The mechanisms leading to malarial anemia are not well understood, although dysregulated immune responses have been implicated. A unique population of inflammatory hemophagocytes that develop in response to Plasmodium yoelii 17XNL infection was recently identified, a nonlethal model of blood stage malaria. The development of these inflammatory hemophagocytes (iHPCs) correlates with anemia and thrombocytopenia, although the mechanisms leading to the development of this novel cell type and its contributions, both direct and indirect, to malarial anemia have yet to be explored. The central hypothesis of this research proposal is that iHPCs differentiate from monocytes in response to cell-intrinsic signaling through Toll-like receptors during infection, and that these cells are responsible for the development of malarial anemia through hemophagocytosis. The proposed research will result in a better understanding of the mechanisms leading to malarial anemia, and has the potential to elucidate possible intervention strategies or therapeutic targets that could reduce illness and mortality during malarial anemia.

Project details

Basic Science

Aug 2020 — Jul 2023

$205,606

United States