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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Bacterial / pharmacology*
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Bacterial Toxins / pharmacology*
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Cells, Cultured
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Cytokines / metabolism*
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Dendritic Cells / drug effects*
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Dendritic Cells / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Humans
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Interleukin-10 / metabolism
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Interleukin-12 / metabolism
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Interleukin-8 / metabolism
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Neutrophil Infiltration / drug effects
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antigens, Bacterial
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Bacterial Toxins
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Cytokines
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Interleukin-8
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Tumor Necrosis Factor-alpha
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anthrax toxin
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Interleukin-10
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Interleukin-12
Grants and funding
This work was supported by grants from Délégation Générale pour l'Armement (CO010808) and Service de Santé des Armées (135OP3B LFR EMA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.