PMID- 26015478 OWN - NLM STAT- MEDLINE DCOM- 20150924 LR - 20181113 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 83 IP - 8 DP - 2015 Aug TI - Micropatterned macrophage analysis reveals global cytoskeleton constraints induced by Bacillus anthracis edema toxin. PG - 3114-25 LID - 10.1128/IAI.00479-15 [doi] AB - Bacillus anthracis secretes the edema toxin (ET) that disrupts the cellular physiology of endothelial and immune cells, ultimately affecting the adherens junction integrity of blood vessels that in turn leads to edema. The effects of ET on the cytoskeleton, which is critical in cell physiology, have not been described thus far on macrophages. In this study, we have developed different adhesive micropatterned surfaces (L and crossbow) to control the shape of bone marrow-derived macrophages (BMDMs) and primary peritoneal macrophages. We found that macrophage F-actin cytoskeleton adopts a specific polar organization slightly different from classical human HeLa cells on the micropatterns. Moreover, ET induced a major quantitative reorganization of F-actin within 16 h with a collapse at the nonadhesive side of BMDMs along the nucleus. There was an increase in size and deformation into a kidney-like shape, followed by a decrease in size that correlates with a global cellular collapse. The collapse of F-actin was correlated with a release of focal adhesion on the patterns and decreased cell size. Finally, the cell nucleus was affected by actin reorganization. By using this technology, we could describe many previously unknown macrophage cellular dysfunctions induced by ET. This novel tool could be used to analyze more broadly the effects of toxins and other virulence factors that target the cytoskeleton. CI - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved. FAU - Trescos, Yannick AU - Trescos Y AD - Unite Interactions Hote-Agents pathogenes, Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France Laboratoire Pathogenie des Toxi-Infections Bacteriennes, Institut Pasteur, Paris, France Ecole du Val-de-Grace, Paris, France. FAU - Tessier, Emilie AU - Tessier E AD - Unite Interactions Hote-Agents pathogenes, Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France. FAU - Rougeaux, Clemence AU - Rougeaux C AD - Unite Interactions Hote-Agents pathogenes, Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France Laboratoire Pathogenie des Toxi-Infections Bacteriennes, Institut Pasteur, Paris, France. FAU - Goossens, Pierre L AU - Goossens PL AD - Laboratoire Pathogenie des Toxi-Infections Bacteriennes, Institut Pasteur, Paris, France. FAU - Tournier, Jean-Nicolas AU - Tournier JN AD - Unite Interactions Hote-Agents pathogenes, Institut de Recherche Biomedicale des Armees, Bretigny-sur-Orge, France Laboratoire Pathogenie des Toxi-Infections Bacteriennes, Institut Pasteur, Paris, France Ecole du Val-de-Grace, Paris, France jntournier.irba@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150526 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Actins) RN - 0 (Antigens, Bacterial) RN - 0 (Bacterial Toxins) RN - 0 (anthrax toxin) SB - IM MH - Actins/metabolism MH - Animals MH - Anthrax/*metabolism/microbiology MH - Antigens, Bacterial/genetics/*metabolism MH - Bacillus anthracis/genetics/*metabolism MH - Bacterial Toxins/genetics/*metabolism MH - Cytoskeleton/*metabolism/microbiology MH - Female MH - Humans MH - Mice, Inbred C57BL PMC - PMC4496603 EDAT- 2015/05/28 06:00 MHDA- 2015/09/25 06:00 PMCR- 2016/02/01 CRDT- 2015/05/28 06:00 PHST- 2015/04/17 00:00 [received] PHST- 2015/05/16 00:00 [accepted] PHST- 2015/05/28 06:00 [entrez] PHST- 2015/05/28 06:00 [pubmed] PHST- 2015/09/25 06:00 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - IAI.00479-15 [pii] AID - 00479-15 [pii] AID - 10.1128/IAI.00479-15 [doi] PST - ppublish SO - Infect Immun. 2015 Aug;83(8):3114-25. doi: 10.1128/IAI.00479-15. Epub 2015 May 26.