Our laboratory has taken advantage of the simple and well-studied nervous and immune systems of C. elegans to study the mechanisms involved in neural-immune communications. Overall, our studies showed that specific genes and neurons in the nervous system of C. elegans control immune responses, indicating that cell non-autonomous signals from different neurons act on non-neural tissues to regulate immune responses at the organismal level (1-4). To study the role of natural genetic variation in the organismal control of immune pathways, we studied C. elegans wild strains isolated from different parts of the world that carry the same mutation in the
npr-1 gene, which encodes a G-protein coupled receptor that participates in a neural circuit that controls not only avoidance to bacterial pathogens but also microbial killing mechanisms that are controlled by the
p38/PMK-1 MAPK immune pathway (1). Interestingly, our studies indicate that 9 wild isolates have evolved mechanisms to compensate for the increased susceptibility to pathogens because of their reduced NPR-1 activity. This highlights the importance of NPR-1 in the control of immunity and provides an opportunity to address which genes and pathways that control immunity in a cell non-autonomous manner may harbor sufficient genetic variation to be targets of natural selection. In order to map and characterize the mechanisms that compensates the effect of the
npr-1 mutation in wild isolates, we are using a combination of whole genome sequencing with a very fine-grained single nucleotide polymorphism mapping strategy (5). Using this approach we rapidly identified a 1 mega base pair locus in chromosome I of one of the environmental isolates that is responsible for the compensatory phenotype. The identification of the responsible gene among the potential candidates is underway. References: 1.Styer et al. Science 322, 460 (Oct 17, 2008); 2.Sun et al. Science 332, 729 (May 6, 2011); 3. Sun et al. EMBO reports 13, 855 (Sep, 2012); 4. Singh and Aballay. J Biol Chem 287, 33191 (Sep 28, 2012); 5. Doitsidou et al. PLoS One 5,
e15435, doi:10.1371/journal.pone.0015435 (2010). Italic Text.