Article
Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium.
Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Current opinion in immunology (impact factor:
10.88).
02/2012;
24(1):3-9.
DOI:10.1016/j.coi.2011.10.004
pp.3-9
Source: PubMed
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Citations (0)
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Article: Stimulation of host immune defenses by a small molecule protects C. elegans from bacterial infection.
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ABSTRACT: The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans-based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens.PLoS Genetics 06/2012; 8(6):e1002733. · 8.69 Impact Factor
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Keywords
basic principles
Caernohabditis elegans
higher order hosts
immune signaling network
Intestinal epithelial cells
intestinal epithelium
nematode
nematodes
simple model system