RRC ID 4225
Author Evans EA, Kawli T, Tan MW.
Title Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans.
Journal PLoS Pathog
Abstract Some pathogens have evolved mechanisms to overcome host immune defenses by inhibiting host defense signaling pathways and suppressing the expression of host defense effectors. We present evidence that Pseudomonas aeruginosa is able to suppress the expression of a subset of immune defense genes in the animal host Caenorhabditis elegans by activating the DAF-2/DAF-16 insulin-like signaling pathway. The DAF-2/DAF-16 pathway is important for the regulation of many aspects of organismal physiology, including metabolism, stress response, longevity, and immune function. We show that intestinal expression of DAF-16 is required for resistance to P. aeruginosa and that the suppression of immune defense genes is dependent on the insulin-like receptor DAF-2 and the FOXO transcription factor DAF-16. By visualizing the subcellular localization of DAF-16::GFP fusion protein in live animals during infection, we show that P. aeruginosa-mediated downregulation of a subset of immune genes is associated with the ability to translocate DAF-16 from the nuclei of intestinal cells. Suppression of DAF-16 is mediated by an insulin-like peptide, INS-7, which functions upstream of DAF-2. Both the inhibition of DAF-16 and downregulation of DAF-16-regulated genes, such as thn-2, lys-7, and spp-1, require the P. aeruginosa two-component response regulator GacA and the quorum-sensing regulators LasR and RhlR and are not observed during infection with Salmonella typhimurium or Enterococcus faecalis. Our results reveal a new mechanism by which P. aeruginosa suppresses host immune defense.
Volume 4(10)
Pages e1000175
Published 2008-10-1
DOI 10.1371/journal.ppat.1000175
PMID 18927620
PMC PMC2568960
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / immunology* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology Down-Regulation / genetics Down-Regulation / immunology Forkhead Transcription Factors Host-Pathogen Interactions / genetics Host-Pathogen Interactions / immunology Immune Tolerance / genetics* Immunity, Innate / genetics Insulin / metabolism Models, Biological Pseudomonas Infections / genetics Pseudomonas Infections / immunology Pseudomonas aeruginosa / pathogenicity Pseudomonas aeruginosa / physiology* Receptor, Insulin / genetics* Receptor, Insulin / metabolism Signal Transduction / genetics Signal Transduction / immunology Transcription Factors / physiology Virulence Factors / physiology
IF 6.218
Times Cited 130
C.elegans tm1907 tm1053