DBLing Your Defenses

Science Signaling  24 Mar 2009:
Vol. 2, Issue 63, pp. ec107
DOI: 10.1126/scisignal.263ec107

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]