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NK Dendritic Cells Are Innate Immune Responders to Listeria monocytogenes Infection¹

Hepatobiliary Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10021

NK dendritic cells (NKDC) are recently described immunologic cells that possess both lytic and Ag-presenting function and produce prolific quantities of IFN-. The role of NKDC in innate immunity to bacterial infection is unknown. Because IFN- is important in the immune response to Listeria monocytogenes (LM), we hypothesized that NKDC play a critical role during LM infection in mice. We found that LM increased the frequency and activation state of NKDC in vivo. Using in vivo intracellular cytokine analysis, we demonstrated that NKDC are a major source of early IFN- during infection with LM. Adoptive transfer of wild-type NKDC into IFN--deficient recipients that were subsequently infected with LM decreased bacterial burden in the liver and spleen and prolonged survival. In contrast, NK cells were depleted early during LM infection, produced less IFN-, and conferred less protection upon adoptive transfer into IFN--deficient mice. In vitro, LM induction of IFN- secretion by NKDC depended on TLR9, in addition to IL-18 and IL-12. Our study establishes NKDC as innate immune responders to bacterial infection by virtue of their ability to secrete IFN-.

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 National Institutes of Health Grants AI70658 and DK068346.

² Address correspondence and reprint requests to Dr. Ronald P. DeMatteo, Memorial Sloan-Kettering Cancer Center, Box 203, 1275 York Avenue, New York, NY 10021. E-mail address: dematter{at}mskcc.org

³ Abbreviations used in this paper: LM, Listeria monocytogenes; NKDC, NK dendritic cells; DC, dendritic cells; WT, wild type; hkLM, heat killed LM; ICC, intracellular cytokine; iCpG, inhibitory CpG.

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