Evidence is accumulating that invertebrates can mount highly specific immune responses that enables them to differentiate between different strains of the same pathogen species. However, the molecular basis of such high immune specificity within the innate immune system is unclear. We were interested in understanding to which level C. elegans specifically responds to infection with two different pathogenic Bacillus thuringiensis (BT) strains. We performed a transcriptome analysis using RNAseq to study the response of C. elegans to three different BT strains, the two pathogenic BT strains MYBT18247 (BT247) and MYBT189679 (BT679), and the non-pathogenic BT407. While the bZIP transcription factor gene
jun-1, which has previously been shown to be important for C. elegans defense against a BT derived toxin, was up-regulated following infection with both pathogenic strains, the GATA transcription factor gene
elt-2 was differentially regulated between BT247 and BT679. We thus further investigated the role of
elt-2 in the C. elegans response to BT infection and found that
elt-2 RNAi treated worms were more resistant on BT247, whereas they were more susceptible on BT679. To gain insight into the mechanism, by which
elt-2 regulates the C. elegans immune response to the different BT strains in such opposite ways, we performed an additional transcriptome analysis on
elt-2 RNAi-treated worms. The genes, which were up-regulated after BT infection under control conditions, but down-regulated in
elt-2 RNAi worms, are enriched for down-stream targets of the
p38 MAPK and DAF-2/insulin-like receptor (ILR) pathways. Survival analysis of the respective pathway mutants revealed that the DAF-2/ILR receptor pathway contributes to resistance on both BT247 and BT679, whereas the
p38 MAPK pathway is exclusively required for resistance on BT679.We propose that C. elegans is able to mount a highly specific immune response to different pathogen strains through the transcription factor gene
elt-2, likely in combination with the
p38 MAPK pathway.