DNA replication and repair are two crucial biological processes that maintain genomic integiry and health of cells. However, very little is known about how these processes are regulated in response to pathogen infection. We have previously shown that NPR-8, a neuronal G protein-coupled receptor, functions in amphid sensory neurons to regulate Caenorhabditis elegans defense against Pseudomonas aeruginosa infection by controlling collagen expression and the dynamics of cuticle structure (Sellegounder et al., Science Advances 2019; 5: eaaw4717). In the current study, we analyzed protein expression in wild-type and
npr-8 mutant animals [
npr-8(
ok1439) null animals] using a mass spectrometry-based quantitative proteomics approach. In total, 1201 proteins were differentially expressed in
npr-8 (
ok1439) animals relative to wild-type animals exposed to P. aeruginosa, among which 74 and 134 proteins were upregulated and downregulated at least 1.5 fold, respectively. While Gene Ontology (GO) analysis of the upregulated genes did not yield any enriched GO terms, GO analysis of the downregulated genes identified 22 enriched biological processes and 8 enriched molecular functions, all of which are related to DNA metabolism. Twelve proteins with functions in DNA replication and repair contribute to these enrichments. Functional assays revealed that P. aeruginosa-infected
npr-8 (
ok1439) animals possess higher DNA double-strand break repair activity than infected wild-type control animals, indicating that NPR-8 suppresses DNA repair activity in wild-type animals in response to infection. How DNA replication activity is affected by the
npr-8 mutation and P. aeruginosa infection as well as whether DNA replication and repair are regulated by the NPR-8-expressing amphid sensory neurons are currently under investigation. Our study suggests that DNA replication and repair processes could be modulated by the nervous system in the defense response to pathogen infection.