Signal transducer and activator of transcription (STAT) transcription factors are important mediators of cytokine signaling and have been implicated in host defense in vertebrates as well as in Drosophila. Here, we show that the function of STATs in regulating immune responses also applies to C. elegans epidermal immunity. The C. elegans epidermis responds to infection with the fungus Drechmeria coniospora and to sterile injury by strongly inducing the expression of antimicrobial peptide genes, including
nlp-29 [1]. We previously isolated nipi (""no induction of peptide after Drechmeria infection"") mutants that fail to express a
pnlp-29::GFP reporter after infection [1]. We cloned
nipi-2 and found that it corresponds to the previously annotated gene
snf-12. It encodes a sodium-dependent neutrotransmitter symporter. We found that
snf-12 cell-autonomously governs
nlp-29 expression in the epidermis. Through epistasis analysis, we placed
snf-12 in the G-protein/PKCdelta/p38 MAPK signaling pathway, previously shown to control epidermal immune signaling in C. elegans [1, 2]. A yeast-two-hybrid screen revealed that the STAT-like transcription factor STA-2 interacts with the C-terminus of SNF-12. We confirmed this interaction by co-IP. Additionally, like
snf-12,
sta-2 mutants have a block in the induction of
nlp-29 following both injury and infection. On the other hand,
sta-2 is not required for the expression of innate immunity genes in the intestine upon PA14 infection, nor for the response to osmotic stress. These results indicate that STA-2 plays a specific role in activating antimicrobial peptide expression in the C. elegans epidermis. 1. Pujol, N., et al., Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol, 2008. 18(7): p. 481-9. 2. Ziegler, K., et al., Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved
p38 MAPK cascade. Cell Host Microbe, 2009. 5(4): p. 341-52.