| Citation | Evans EA, Kawli T, Tan MW. Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. PLoS Pathog, 2008. |
| PubMed ID | 18927620 |
| Short Description | Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. GEO Record: GSE13473 Platform: GPL7559 GPL7560 GPL7561 GPL7562 Download gene-centric, log2 transformed data: WBPaper00032276.ce.mr.csv |
| # of Conditions | 26 |
Full Description
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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. Experimental Details: WBPaper00032276:op50_0421_N2_24h WBPaper00032276:daf-2_OP50_1 WBPaper00032276:op50_0529_N2_4h WBPaper00032276:pa14_0421_N2_24h WBPaper00032276:daf-2_PA14_4 WBPaper00032276:pa14_sma6_0730_4h WBPaper00032276:pa14_0422_N2_24h WBPaper00032276:daf-2_PA14_2 WBPaper00032276:pa14_0629_4hr WBPaper00032276:pa14_0423_N2_24h WBPaper00032276:pa14_sma6_0702_4h WBPaper00032276:op50_0507_N2_4h WBPaper00032276:op50_0422_N2_24h WBPaper00032276:daf-2_OP50_3 WBPaper00032276:daf-2_PA14_3 WBPaper00032276:op50_0629_N2_4h WBPaper00032276:op50_0429_sma6_4h WBPaper00032276:pa14_0507_N2_4h WBPaper00032276:daf-2_PA14_1 WBPaper00032276:daf-2_OP50_4 WBPaper00032276:op50_sma6_0702_4h WBPaper00032276:pa14_0429_sma6_4h WBPaper00032276:op50_sma6_0730_4h WBPaper00032276:pa14_0529_N2_4h WBPaper00032276:op50_N2_1119_24h WBPaper00032276:daf-2_OP50_2. |
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