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

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 prog...

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Main Authors: Saida Benomar, Patrick Lansdon, Aaron M Bender, Blake R Peterson, Josephine R Chandler, Brian D Ackley
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-01-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1008134
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author Saida Benomar
Patrick Lansdon
Aaron M Bender
Blake R Peterson
Josephine R Chandler
Brian D Ackley
author_facet Saida Benomar
Patrick Lansdon
Aaron M Bender
Blake R Peterson
Josephine R Chandler
Brian D Ackley
author_sort Saida Benomar
collection DOAJ
description 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.
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spelling doaj.art-51b0401b71c24aafb24cf5aabf52ffb82022-12-21T22:36:13ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-01-01161e100813410.1371/journal.ppat.1008134The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.Saida BenomarPatrick LansdonAaron M BenderBlake R PetersonJosephine R ChandlerBrian D AckleyCaenorhabditis 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.https://doi.org/10.1371/journal.ppat.1008134
spellingShingle Saida Benomar
Patrick Lansdon
Aaron M Bender
Blake R Peterson
Josephine R Chandler
Brian D Ackley
The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
PLoS Pathogens
title The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
title_full The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
title_fullStr The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
title_full_unstemmed The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
title_short The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
title_sort c elegans chp1 homolog pbo 1 functions in innate immunity by regulating the ph of the intestinal lumen
url https://doi.org/10.1371/journal.ppat.1008134
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