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Both lethal and edema toxins of Bacillus anthracis disrupt the human dendritic cell chemokine network

Cleret-Buhot, A;Mathieu, J;Tournier, JN;Quesnel-Hellmann, A;

Bacillus anthracis, the agent of anthrax, produces two main virulence factors: a capsule and two toxins. Both lethal toxin (LT) and edema toxin (ET) paralyze the immune defense system. Here, we analyze the effects of LT and ET on the capacity of human monocyte-derived dendritic cells (MoDC) to produce proinflammatory chemokines. We show that both toxins disrupt proinflammatory chemokine production. LT has more pronounced effects than ET on CXCL8 production, which is correlated with impaired recruitment of neutrophils in vitro. Finally, we show that both toxins also differentially disrupt IL-12p70, IL-10, and TNF- production. Taken together, these results demonstrate that both B. anthracis toxins alter MoDC functions and the activation of the innate immune system.