Migrating monocytes recruited to the spleen play an important role in control of blood stage malaria.

Abstract

Host responses controlling blood-stage malaria include both innate and acquired immune effector mechanisms. During Plasmodium chabaudi infection in mice, a population of CD11b(high)Ly6C(+) monocytes are generated in bone marrow, most of which depend on the chemokine receptor CCR2 for migration from bone marrow to the spleen. In the absence of this receptor mice harbor higher parasitemias. Most importantly, splenic CD11b(high)Ly6C(+) cells from P chabaudi-infected wild-type mice significantly reduce acute-stage parasitemia in CCR2(-/-) mice. The CD11b(high)Ly6C(+) cells in this malaria infection display effector functions such as production of inducible nitric oxide synthase and reactive oxygen intermediates, and phagocytose P chabaudi parasites in vitro, and in a proportion of the cells, in vivo in the spleen, suggesting possible mechanisms of parasite killing. In contrast to monocyte-derived dendritic cells, CD11b(high)Ly6C(+) cells isolated from malaria-infected mice express low levels of major histocompatibility complex II and have limited ability to present the P chabaudi antigen, merozoite surface protein-1, to specific T-cell receptor transgenic CD4 T cells and fail to activate these T cells. We propose that these monocytes, which are rapidly produced in the bone marrow as part of the early defense mechanism against invading pathogens, are important for controlling blood-stage malaria parasites.

• Authors: Anne-Marit Sponaas, Ana Paula Freitas do Rosario, Cecile Voisine, Beatris Mastelic, Joanne Thompson, Sandra Koernig, William Jarra, Laurent Renia, Marjorie Mauduit, Alexandre J Potocnik, Jean Langhorne
• Journal: Blood (Blood) Vol. 114 Issue 27 Pg. 5522-31 (Dec 24 2009) ISSN: 1528-0020 [Electronic] United States
• PMID: 19837977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Ly
• CD11b Antigen
• Ccr2 protein, mouse
• Ly-6C antigen, mouse
• Receptors, CCR2
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II

Topics

• Animals
• Antigen-Presenting Cells (metabolism, parasitology, pathology)
• Antigens, Ly (metabolism)
• CD11b Antigen (metabolism)
• CD4-Positive T-Lymphocytes (metabolism, parasitology, pathology)
• Cell Movement (physiology)
• Flow Cytometry
• Host-Parasite Interactions
• Malaria (blood, parasitology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (metabolism, parasitology, pathology)
• Nitric Oxide Synthase Type II (metabolism)
• Parasitemia (metabolism)
• Phagocytosis (physiology)
• Plasmodium chabaudi (physiology)
• Receptors, CCR2 (genetics, metabolism)
• Spleen (metabolism, parasitology, pathology)
• T-Lymphocytes (metabolism, parasitology, pathology)
• Tumor Necrosis Factor-alpha (metabolism)