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

English version

Autoři: Saida Benomar ^aff001; Patrick Lansdon ^aff001; Aaron M. Bender ^aff002; Blake R. Peterson ^aff002; Josephine R. Chandler ^aff001; Brian D. Ackley ^aff001
Působiště autorů: Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, United States of America ^aff001; Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS, United States of America ^aff002
Vyšlo v časopise: The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008134
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1008134

Souhrn

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 Ca²⁺-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 H₂O_2, in response to pathogens, which is an important component of pathogen defense. We show that pbo-1 mutants exhibited decreased H₂O₂ 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.

Klíčová slova:

Bacterial pathogens – Pseudomonas aeruginosa – Pathogens – Caenorhabditis elegans – Gastrointestinal tract – Animal pathogens – Enterococcus faecalis – Bicarbonates

Zdroje

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