Infection of worms by the fungus Drechmeria coniospora leads to an innate immune reaction involving the rapid up-regulation of members of the nlp and cnc/caenacin gene families that encode antimicrobial peptides (AMPs). We previously reported that the expression upon infection of one of these peptides, NLP-29, requires TIR-1, a homologue of SARM, a Toll/interleukin 1 receptor (TIR)-domain protein (1) that acts upstream of a NSY1/SEK-1/PMK-1
p38 MAPK signalling pathway in bacterial resistance and neuronal development (2, 3). Many of the infection-inducible nlp and cnc genes are found in two distinct genomic clusters on the left arm of chromosome V. Phylogenetic analysis revealed that these AMPs form an exclusive monophylic group separated from the other nlp genes. Within this monophylum, almost all the cnc genes cluster together. Furthermore, the genes
nlp-27 to
nlp-31 form a well-supported clade. Searches in available genomic sequence of related nematodes C. briggsae and C. remanei reveal that AMP genes of the
nlp-29 cluster specifically expanded in C. elegans and are evolving under positive selection. Strikingly, we show that all members of this cluster are up-regulated by infection in a
p38-dependent manner, but differ in their response to wounding and osmotic stress. For example, unlike
nlp-29 (see abstract by Pujol et al.),
nlp-30 is upregulated by infection and wounding, but not under high salt conditions. In clear contrast to
nlp-29 and
nlp-30,
cnc-2 is neither induced by wounding nor osmotic stress. Moreover, the induction of
cnc-2 seen upon fungal infection is independent of a
p38 signalling pathway but appears to involve an uncharacterised non-canonical TGF-<font face=symbol>b</font> pathway as it requires SMA-6, but not the known SMAD complex. Although
daf-2 mutants are more resistant to Drechmeria infection, unexpectedly, the expression of both
nlp-29 and
cnc-2 is abrogated in a
daf-2 mutant, in a
daf-16-dependent fashion. Thus distinct stimuli, including infection, osmotic stress and wounding, induce the up-regulation of different AMPs using genetically separable signalling pathways. These results bring to light an unexpected complexity of AMP gene regulation in C. elegans. 1. Couillault et al (2004) Nat Immunol 5, 488-494. 2. Chuang, & Bargmann (2005) Genes Dev 19, 270-81. 3. Liberati et al (2004) Proc Natl Acad Sci U S A 101, 6593-8.