Abstract
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-α production. Taken together, these results demonstrate that both B. anthracis toxins alter MoDC functions and the activation of the innate immune system.
Highlights
Successful colonization of a host by pathogens relies on their capacity to evade the complex defenses created by the immune system
We focus on human monocyte-derived dendritic cells (MoDC) infected by mutants of Bacillus anthracis expressing lethal toxin (LT), edema toxin (ET), or both, and a nontoxinogenic mutant to evaluate the effects of LT and ET on chemokine production
Generation of MoDCs MoDCs were generated from human peripheral blood mononuclear cells (PBMC) from healthy donors provided by the Etablissement Francais du Sang (EFS)
Summary
Successful colonization of a host by pathogens relies on their capacity to evade the complex defenses created by the immune system. The agent of anthrax, has developed efficient strategies to overcome the host immune defenses, which include in particular two toxins: lethal toxin (LT) and edema toxin (ET), which are formed, respectively, by a protective antigen (PA) component associated with lethal factor (LF) or edema factor (EF) [1]. The binding moiety PA interacts with one of the two anthrax cell receptors: ANTXR1 or Tumor Endothelial Marker-8 (TEM8) and ANTXR2 or Capillary Morphogenesis Protein-2 (CMG-2) [1]. Of importance is the fact that more innate immune cells belonging to the NK family have been recently added to the toxin target list, thereby improving our knowledge of the interactions between B. anthracis and the immune system [5,6]. Important information has been revealed recently by using myeloid-specific CMG2 knockout mice, this showing that impairment of myeloid cells by both toxins is critical for the establishment of the disease [7]
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