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Dendritic Cells Expressing Plasmacytoid Marker PDCA-1 Are Trojan Horses during Toxoplasma gondii Infection¹

Allison L. Bierly^*, William J. Shufesky, Woraporn Sukhumavasi^*, Adrian E. Morelli and Eric Y. Denkers^2,*

^* Department of Microbiology and Immunology, Cornell University College of Veterinary Medicine, Ithaca, NY 14853; and Thomas E. Starzl Transplantation Institute, Department of Surgery and Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

Plasmacytoid dendritic cells (pDCs) play a key role in the innate immune response to viral infection, due largely to their ability to produce large quantities of type I IFNs. These cells are also notable for their ability to differentiate into conventional dendritic cells after appropriate stimulation. Here, we show that a splenic population of murine CD11c⁺ cells expressing pDC markers Gr-1, B220, and PDCA-1 is preferentially parasitized after infection with the virulent RH strain of Toxoplasma gondii. Although these markers are closely associated with pDCs, the population we identified was unusual because the cells express CD11b and higher than expected levels of CD11c. By adoptive transfer of CD45.1-positive cells into CD45.2 congenic mice, we show that CD11c⁺Gr-1⁺ cells migrate from the peritoneal cavity to the spleen. During infection, these cells accumulate in the marginal zone region. Recruitment of infected CD11c⁺Gr-1⁺ cells to the spleen is partially dependent upon signaling through chemokine receptor CCR2. Intracellular cytokine staining demonstrates that infected, but not noninfected, splenic CD11c⁺Gr-1⁺ dendritic cells are suppressed in their ability to respond to ex vivo TLR stimulation. We hypothesize that Toxoplasma exploits pDCs as Trojan horses, targeting them for early infection, suppressing their cytokine effector function, and using them for dissemination within the host.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grants AI50617 (E.Y.D.), T32 AI07643 (A.L.B.) and HL075512 and HL077545 (A.E.M.).

² Address correspondence and reprint requests to E. Denkers, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853. E-mail address: eyd1{at}cornell.edu

³ Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DCs; DAPI, 4',6'-diamidino-2-phenylindole.

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