both lethal and edema toxins of bacillus anthracis disrupt the human dendritic cell chemokine network致命和水肿的炭疽杆菌毒素破坏人类的树突细胞趋化因子网络.pdfVIP

Both Lethal and Edema Toxins of Bacillus anthracis Disrupt the Human Dendritic Cell Chemokine Network ´ ¤ Aurelie Cleret-Buhot , Jacques Mathieu, Jean-Nicolas Tournier, Anne Quesnel-Hellmann* ´ ˆ ` ´ ´ ´ Unite Interactions Hote-Agents Pathogenes, Departement de Microbiologie, Institut de Recherche Biomedicale des Armees, La Tronche, France 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-a production. Taken together, these results demonstrate that both B. anthracis toxins alter MoDC functions and the activation of the innate immune system. Citation: Cleret-Buhot A, Mathieu J, Tournier J-N, Quesnel-Hellmann A (2012) Both Lethal and Edema Toxins of Bacillus anthracis Disrupt the Human Dendritic Cell Chemokine Network. PLoS ONE 7(8): e43266. doi:10.1371/journal.pone.0043266 Editor: Prosper N. Boyaka, The Ohio State University, United States of America Received May 15, 2012; Accepted July 18, 2012; Published August 24, 2012 Copyright: 2012 Cleret-Buhot et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original a