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* Département de Biologie des Agents Transmissibles, Centre de Recherches du Service de Santé des Armées, La Tronche, France;
Department of Experimental Biomedical Sciences, University of Padova, Padova, Italy;
Ben-May Institute for Cancer Research, University of Chicago, Chicago, IL 60637; and
Toxines et Pathogénie Bactérienne (Unité de Recherche Associée 2172, Centre National de la Recherche Scientifique), Institut Pasteur, Paris, France
Bacillus anthracis secretes two critical virulence factors, lethal toxin (LT) and edema toxin (ET). In this study, we show that murine bone marrow-derived dendritic cells (DC) infected with B. anthracis strains secreting ET exhibit a very different cytokine secretion pattern than DC infected with B. anthracis strains secreting LT, both toxins, or a nontoxinogenic strain. ET produced during infection selectively inhibits the production of IL-12p70 and TNF-
, whereas LT targets IL-10 and TNF- production. To confirm the direct role of the toxins, we show that purified ET and LT similarly disrupt cytokine secretion by DC infected with a nontoxinogenic strain. These effects can be reversed by specific inhibitors of each toxin. Furthermore, ET inhibits in vivo IL-12p70 and IFN-
secretion induced by LPS. These results suggest that ET produced during infection impairs DC functions and cooperates with LT to suppress the innate immune response. This may represent a new strategy developed by B. anthracis to escape the host immune response.
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