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Published online before print September 12, 2003

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0403164

Received for publication April 18, 2003.
Revised July 28, 2003.
Accepted for publication July 29, 2003.

Article

A novel population of Gr-1⁺-activated macrophages induced during acute toxoplasmosis

Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri

^@ To whom correspondence should be addressed. E-mail: sibley{at}borcim.wustl.edu.

	Abstract

Macrophages are potent mediators of parasite control following in vitro activation, yet the subsets of mononuclear cells that contribute to resistance in vivo remain poorly defined. To identify effector cells that contribute to the control of Toxoplasma gondii during the initial stages of disseminated infection, we developed a low-dose intraperitoneal challenge model. A population of unusual macrophage-like cells was recruited to the peritoneal cavity during the first 4 days postinfection. Surprisingly, these cells expressed the granulocyte marker Gr-1 and the macrophage marker CD68. They also expressed high levels of major histocompatibility complex class II and low levels of F4/80 and CD11b and were negative for the immature myeloid cell marker CD31, the dendritic cell marker CD11c, and the B cell marker B220. Gr-1⁺ macrophages produced interleukin-12 p40, generated reactive nitrogen intermediates during acute infection, and inhibited virulent type I and nonvirulent type II strains of the parasite in vitro. Gr-1⁺ macrophages were the primary cell type recruited in response to nonvirulent type II strain parasites, and large numbers of neutrophils (Gr-1⁺/CD68^-) were also recruited to the peritoneum in response to virulent type I strain parasites. Our findings suggest that activated CD68⁺/Gr-1⁺ macrophages contribute to parasite control during infection by directly inhibiting parasite replication and through production of T helper cell type I cytokines.

Key Words: host defense • intracellular pathogen • neutrophils • cellular activation • dendritic cells

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