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Background  Resistance to enteric pathogens is a complex trait at the crossroads of multiple biological processes. We have previously shown in the  Drosophila  Genetic Reference Panel (DGRP) that resistance to infection is highly heritable, but our understanding of how the effects of genetic variants affect different molecular mechanisms to determine gut immunocompetence is still limited.    Results  To address this, we perform a systems genetics analysis of the gut transcriptomes from 38 DGRP lines that were orally infected with  Pseudomonas entomophila . We identify a large number of condition-specific, expression quantitative trait loci ( local -eQTLs) with infection-specific ones located in regions enriched for FOX transcription factor motifs. By assessing the allelic imbalance in the transcriptomes of 19 F1 hybrid lines from a large round robin design, we independently attribute a robust  cis -regulatory effect to only 10% of these detected  local -eQTLs. However, additional analyses indicate that many  local -eQTLs may act in  trans  instead. Comparison of the transcriptomes of DGRP lines that were either susceptible or resistant to  Pseudomonas entomophila  infection reveals  nutcracker  as the only differentially expressed gene. Interestingly, we find that  nutcracker  is linked to infection-specific eQTLs that correlate with its expression level and to enteric infection susceptibility. Further regulatory analysis reveals one particular eQTL that significantly decreases the binding affinity for the repressor Broad, driving differential allele-specific  nutcracker  expression.    Conclusions  Our collective findings point to a large number of infection-specific  cis-  and  trans- acting eQTLs in the DGRP, including one common non-coding variant that lowers enteric infection susceptibility.

cis-regulatory variation modulates susceptibility to enteric infection in the Drosophila genetic reference panel