Drosophila melanogaster has proven to be a useful model system for elucidating the pathways of innate immunity, but could worms become the new Drosophila? A new study shows that worms, although they lack the Toll and Imd pathways by which Drosophila respond to bacterial and fungal infections, can produce antimicrobial peptides in response to infection.

The authors used a microarray strategy to identify genes induced in worms after infection with the fungus Drechmeria coniospora and the Gram-negative bacterium Serratia marcescens. Only two genes (nlp-29 and cnc-2), which encode peptide molecules, were strongly induced by both infections. An additional four genes were induced after infection with D. coniospora. A representative member of the peptide family, neuropeptide-like protein-31 (nlp-31), was synthesized and found to have antifungal activity in vitro.

To study the induction of these peptides in vivo, transgenic worms were generated expressing green fluorescent protein under control of the nlp-29 and nlp-31 promoters. Expression of nlp-31 in the hypodermis increased after D. coniospora infection. In addition to the hypodermal expression, localized expression was observed in the nlp-29-transgenic worms in the vulval region where the fungal spores adhered.

Worms have a single Toll-like receptor gene, tol-1 . So, does tol-1 control expression of the antimicrobial peptides? Tol-1 mutants were no more susceptible than wild-type worms to infection with D. coniospora, indicating that tol-1 does not control antifungal defence. But worms have an additional gene that encodes another Toll/interleukin-1 receptor (TIR)-domain-containing protein. The authors called this gene tir-1. Of the five possible isoforms, tir-1a is a homologue of the vertebrate TIR-domain-containing adaptor protein SARM (sterile α and armadillo motif protein), the function of which is unknown. When tir-1 was inactivated by RNA interference, the worms were more susceptible to infection, and production of the antimicrobial peptides was reduced. Because tol-1 has no role in regulating peptide expression, it seems that tir-1 is not coupled to an upstream TIR-domain-containing receptor, and the authors suggest that this might also be the case for SARM.

To characterize tir-1 interactions, a yeast two-hybrid screen was carried out. Eight proteins, as well as tir-1, were identified in this screen. Two of these genes, corresponding to the small GTPase Rab1 and the f-subunit of ATP synthase, were required for expression of the antimicrobial peptides, although how these interactions control peptide expression has yet to be determined.