title: Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells.
abstract: 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-alpha, whereas LT targets IL-10 and TNF-alpha 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-gamma 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.
authors.affiliation: Département de Biologie des Agents Transmissibles, Centre de Recherches du Service de Santé des Armées, La Tronche Cedex, France. jntournier@crssa.net
authors.forename: Jean-Nicolas
authors.initials: JN
authors.lastname: Tournier
authors.forename: Anne
authors.initials: A
authors.lastname: Quesnel-Hellmann
authors.forename: Jacques
authors.initials: J
authors.lastname: Mathieu
authors.forename: Cesare
authors.initials: C
authors.lastname: Montecucco
authors.forename: Wei-Jen
authors.initials: WJ
authors.lastname: Tang
authors.forename: Michèle
authors.initials: M
authors.lastname: Mock
authors.forename: Dominique R
authors.initials: DR
authors.lastname: Vidal
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Goossens
mesh_terms: D000262:Adenylyl Cyclases / Q000633:toxicity*; D000818:Animals; D000942:Antigens, Bacterial / Q000633:toxicity*; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D021122:Protein Subunits / Q000096:biosynthesis; D013171:Spores, Bacterial / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D021122:Protein Subunits; D014409:Tumor Necrosis Factor-alpha; C030325:anthrax toxin; D016753:Interleukin-10; D018664:Interleukin-12; D000262:Adenylyl Cyclases