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Sci. Signal., 24 March 2009
Vol. 2, Issue 63, p. ec107
[DOI: 10.1126/scisignal.263ec107]

EDITORS' CHOICE

Immunology DBLing Your Defenses

Elizabeth M. Adler

Science Signaling, AAAS, Washington, DC 20005, USA

The nematode Caenorhabditis elegans responds to infection by the pathogenic fungus Drechmeria coniospora by increasing the expression of genes encoding antimicrobial peptides; among these are several genes in the nlp family (the nlp-29 cluster) whose induction depends on a cell-autonomous p38 mitogen-activated protein kinase signaling pathway. Zugasti and Ewbank explored the generalizability of this response by investigating the regulation of a group of genes in the caenacin (cnc) family (the cnc-2 cluster) that are structurally and phylogenetically related to the nlp genes and are also induced by D. coniospora infection. Transgenic worms with additional copies of cnc-2 cluster genes showed increased survival after D. coniospora infection compared with wild-type worms, consistent with a role in antifungal defense, but failed to show increased resistance to bacterial pathogens. Five of six cnc-2 cluster genes were induced by D. coniospora infection; however, unlike the nlp genes, infection-mediated induction of cnc-2 cluster gene expression was independent of the p38 homolog PMK-1. Analysis of a fluorescent reporter indicated that cnc-2 induction in response to D. coniospora infection was reduced or abolished in worms lacking DBL-1, a transforming growth factor–β (TGF-β) homolog. DBL-1 acts through a SMA-6-DAF-4 heterodimer to regulate C. elegans body size, and loss of either of these transmembrane kinases blocked infection-dependent induction of the cnc-2 reporter. Noting that cnc-2 is expressed in epidermis, whereas SMA-6 is found in epidermis and intestine, the authors showed that expression of sma-6 in epidermis, but not intestine, mediated infection-dependent induction of cnc-2 expression. DBL-1–dependent regulation of body size depends on the three Smad homologs SMA-2, SMA-3, and SMA-4; however, only SMA-3 was required for the response to infection. DBL-1 is produced mainly in the nervous system, and experiments with transgenic worms confirmed that neuronally produced DBL-1 promoted infection-dependent expression of epidermal cnc-2. Thus, in contrast to the nlp-mediated response to fungal infection, cnc-2 induction depends on a neuronal signal mediated through a noncanonical TGF-β signaling pathway.

O. Zugasti, J. J. Ewbank, Neuroimmune regulation of antimicrobial peptide expression by a noncanonical TGF-β signaling pathway in Caenorhabditis elegans epidermis. Nat. Immunol. 10, 249–256 (2009). [PubMed]

Citation: E. M. Adler, DBLing Your Defenses. Sci. Signal. 2, ec107 (2009).


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