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


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
doi: 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 H2O2, 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:

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


Zdroje

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