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CD11c⁺ Dendritic Cells Are Required for Survival in Murine Polymicrobial Sepsis¹

Philip O. Scumpia^*, Priscilla F. McAuliffe^*, Kerri A. O’Malley^*, Ricardo Ungaro^*, Takefumi Uchida^*, Tadashi Matsumoto^*, Daniel G. Remick, Michael J. Clare-Salzler, Lyle L. Moldawer^2,* and Philip A. Efron^*

^* Department of Surgery and Department of Pathology, University of Florida, Gainesville, FL 32610; and Department of Pathology, University of Michigan, Ann Arbor, MI 48103

CD11c⁺ dendritic cells (DCs) are APCs that link innate and adaptive immunity. Although DCs are lost from spleen and lymph nodes in sepsis, their role in outcome remains unclear. Transgenic mice (B6.FVB-Tg^{.Itgax-DTR/EGFP.57}Lan/J) expressing the diphtheria toxin (DT) receptor on the CD11c promoter (DCKO mice) received 4 ng/kg DT, which resulted in depletion of 88–95% of mature myeloid and lymphoid DCs, with less depletion (75%) of plasmacytoid DCs. Pretreatment of DCKO mice with DT resulted in reduced survival in sepsis compared with saline-pretreated DCKO mice (0 vs 54%; p < 0.05) or DT-treated wild-type littermates (0 vs 54%; p < 0.05). This increased mortality was not associated with either increased bacteremia or plasma cytokine concentrations. Intravenous injection of 10⁷ wild-type DCs improved survival in DCKO mice (42 vs 0%; p = 0.05). These data confirm that DCs are essential in the septic response and suggest that strategies to maintain DC numbers or function may improve outcome.

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