Rac2 is a major actor of Drosophila resistance to Pseudomonas aeruginosa acting in phagocytic cells.
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.
Avet-Rochex
Amélie
A
Commissariat à l'Energie Atomique, DSV, iRTSV, 17 rue des Martyrs, Grenoble F-38054, France.
Perrin
Jackie
J
Bergeret
Evelyne
E
Fauvarque
Marie-Odile
MO
D036002:ADP Ribose Transferases / Q000378:metabolism*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D001427:Bacterial Toxins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism / Q000382:microbiology*; D006090:Gram-Negative Bacteria / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D008954:Models, Biological; D010587:Phagocytosis; D010950:Plasma Cells / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D018805:Sepsis; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*; D000097766:RAC2 GTP-Binding Protein
D036002:ADP Ribose Transferases; D023181:Antimicrobial Cationic Peptides; D001427:Bacterial Toxins; D048055:Mitogen-Activated Protein Kinase 8; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C444820:exoenzyme S