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Rac2 is a major actor of Drosophila resistance to Pseudomonas aeruginosa acting in phagocytic cells.

Abstract : Pathogen recognition and engulfment by phagocytic cells of the blood cell lineage constitute the first line of defense against invading pathogens. This cellular immune response is conserved throughout evolution and depends strictly on cytoskeletal changes regulated by the RhoGTPases family. Many pathogens have developed toxins modifying RhoGTPases activity to their own benefit. In particular, the Exoenzyme S (ExoS) toxin of the Gram-negative bacteria Pseudomonas aeruginosa is directly injected into the host cell cytoplasm and contains a GAP domain (ExoSGAP) targeting RhoGTPases. Searching for the contribution of each RhoGTPases, Rho1, Rac1, Rac2, Mtl (Mig2-like) and Cdc42 to fly resistance to P. aeruginosa infections, we found that Rac2 is required to resist to P. aeruginosa and to other Gram-negative or Gram-positive bacteria. The Rac2 immune-deficient phenotype is attributable to defective engulfment of pathogens since Rac2-mutant macrophages exhibited strong reduction in the phagocytosis level of both Gram-negative and Gram-positive bacterial particles whereas systemic immune signaling pathways, including Toll, Immune deficiency and Jun kinases, were not affected. Co-expression of Rac2 and ExoSGAP rescued the increased sensitivity to P. aeruginosa observed in ExoSGAP-expressing flies suggesting that Rac2 is the main host factor whose function is inhibited by the GAP domain of the ExoS toxin.
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Contributor : Marie-Odile Fauvarque Connect in order to contact the contributor
Submitted on : Monday, July 27, 2009 - 4:27:15 PM
Last modification on : Friday, November 6, 2020 - 4:15:51 AM

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Amélie Avet-Rochex, Jackie Perrin, Evelyne Bergeret, Marie-Odile Fauvarque. Rac2 is a major actor of Drosophila resistance to Pseudomonas aeruginosa acting in phagocytic cells.. Genes to Cells, Wiley, 2007, 12 (10), pp.1193-204. ⟨10.1111/j.1365-2443.2007.01121.x⟩. ⟨inserm-00407800⟩



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