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Worms produce surprise insight into human fever

Give or take a few dozen trillions, a human adult has about 70 trillion cells. An adult Caenorhabditis elegans roundworm has exactly 959 cells.

Yet we have an awful lot in common, says Alejandro Aballay of Duke University, who has been exploring two “highly conserved? cell-signaling pathways for innate immunity shared by worms and humans. For one, we have a lot of common enemies, particularly soil-borne pathogens. C. elegans, of course, lives in the soil. Human populations merely ingest soil by the ton in our food, on our hands, and suspended in our drinking water.

Some of these basic pathways that set off the worm’s innate immune defenses have homologs—similar proteins in mammal cells, including ours. These conserved pathways are involved in many similar “effector?strategies against hostile bugs peristalsis, low gut pH, lytic enzymes, and antimicrobial peptides to prevent microbial colonization of the intestine.

In dissecting two conserved pathways required for C. elegans immunity to bacteria, Aballay found a wealth of data on innate immunity plus a surprising insight into another classic metazoan response to infection fever.

The first pathway was p38 MAPK/CED-3, which is also required for the activation of programmed cell death under certain stresses. The other was a heat shock transcription factor-1 (HSF-1) pathway, which is elicited by increased temperature independently of p38 MAPK/CED-3. Aballay identified genes in both pathways that encoded immunity effector molecules plus relevant signaling molecules and transcription factors. In fluorescently labeled transgenic worms, he mapped gene expression in the two target pathways as they came into direct contact with a small zoo of pathogenic microbes.

The big surprise was the discovery that the HSF-1 pathway was required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis. It in
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Source:American Society for Cell Biology


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