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Caenorhabditis elegans  are soil-dwelling nematodes and models for understanding innate immunity and infection. Previously, we developed a novel fluorescent dye (KR35) that accumulates in the intestine of  C .  elegans  and reports a dynamic wave in intestinal pH associated with the defecation motor program. Here, we use KR35 to show that mutations in the Ca 2+ -binding protein, PBO-1, abrogate the pH wave, causing the anterior intestine to be constantly acidic. Surprisingly,  pbo-1  mutants were also more susceptible to infection by several bacterial pathogens. We could suppress pathogen susceptibility in  pbo-1  mutants by treating the animals with pH-buffering bicarbonate, suggesting the pathogen susceptibility is a function of the acidity of the intestinal pH. Furthermore, we use KR35 to show that upon infection by pathogens, the intestinal pH becomes neutral in a wild type, but less so in  pbo-1  mutants.  C .  elegans  is known to increase production of reactive oxygen species (ROS), such as H 2 O 2,  in response to pathogens, which is an important component of pathogen defense. We show that  pbo-1  mutants exhibited decreased H 2 O 2  in response to pathogens, which could also be partially restored in  pbo-1  animals treated with bicarbonate. Ultimately, our results support a model whereby PBO-1 functions during infection to facilitate pH changes in the intestine that are protective to the host.

The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen