Daniel Wong, Katja Ziegler, C. Lopold Kurz, Nathalie Pujol & Jonathan Ewbank Using cDNA microarrays developed by Yuji Kohara, we previously showed that infection of worms by the bacterial pathogen Serratia marcescens and the fungus Drechmeria coniospora provoke the upregulation of distinct sets of antimicrobial genes (1, 2). We have now extended this analysis, using whole genome long oligo microarrays, to a number of other bacterial pathogens. We found that each pathogen elicits a specific transcriptional response.. We have also used microarrays to analyse the transcription response of nipi1 and nipi3 (see abstract by Pujol et al.) to fungal infection. In addition to an abrogation of induction of the
nlp-29 gene that encodes an antimicrobial peptide (AMP), a number of other AMP genes (cnc and nlp, as well as novel putative AMP genes) show an altered expression in the nipi mutants.. We have taken a candidate gene approach to investigate signalling pathways involved in AMP regulation, using the IG274 strain and the Union Biometrica COPAS sorter (see abstract by Pujol et al.). Full induction of
pnlp-29::GFP requires the NSY1/SEK-1/PMK-1 MAPK pathway that has been shown to act in the intestine to protect worms from infection by Pseudomonas aeruginosa (3). It does not require
kgb-1 or
jkk-1 activity, but is partially dependent on the MAP2K
mek-1. Induction of
pnlp-29::GFP is also strongly dependent upon the TIR-domain adapter protein TIR-1 that is upstream of NSY-1 (2,4). The TIR-1/MAPK pathway also has a role in neuronal cell fate determination, acting downstream of
unc-43 (5), but
unc-43 mutants exhibit normal expression of
pnlp-29::GFP. It is therefore not known what lies upstream of
tir-1 in the AMP-activation pathway, nor how infection is recognised in C. elegans. We will report on our ongoing bioinformatics analyses of the transcriptional response of worms to infection that we hope will reveal the underlying signalling networks required for innate immune defence.. 1. Mallo et al. Curr Biol 12, 1209 (2002). 2. Couillault et al. Nat Immunol 5, 488 (2004).. 3. Kim et al. Science 297, 623 (2002). 4. Liberati et al. PNAS 101, 6593 (2004). 5. Chuang & Bargmann Genes Dev 19, 270 (2005).