The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
25
09
2018
accepted:
07
10
2019
entrez:
10
1
2020
pubmed:
10
1
2020
medline:
28
4
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31917826
doi: 10.1371/journal.ppat.1008134
pii: PPATHOGENS-D-18-01864
pmc: PMC6952083
doi:
Substances chimiques
Bicarbonates
0
Caenorhabditis elegans Proteins
0
PBO-1 protein, C elegans
0
Calcineurin
EC 3.1.3.16
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008134Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM113117
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103418
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133572
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103638
Pays : United States
Organisme : NIGMS NIH HHS
ID : K12 GM063651
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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