Blood Group O-Dependent cellular responses to cholera toxin: Parallel clinical and epidemiological links to severe cholera

F. Matthew Kuhlmann, Srikanth Santhanam, Pardeep Kumar, Qingwei Luo, Matthew A. Ciorba, James M. Fleckenstein

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Because O blood group has been associated with more severe cholera infections, it has been hypothesized that cholera toxin (CT) may bind non-O blood group antigens of the intestinal mucosae, thereby preventing efficient interaction with target GM1 gangliosides required for uptake of the toxin and activation of cyclic adenosine monophosphate (cAMP) signaling in target epithelia. Herein, we show that after exposure to CT, human enteroids expressing O blood group exhibited marked increase in cAMP relative to cells derived from blood group A individuals. Likewise, using CRISPR/Cas9 engineering, a functional group O line (HT-29-A-/-) was generated from a parent group A HT-29 line. CT stimulated robust cAMP responses in HT-29-A-/- cells relative to HT-29 cells. These findings provide a direct molecular link between blood group O expression and differential cellular responses to CT, recapitulating clinical and epidemiologic observations.

Original languageEnglish
Pages (from-to)440-443
Number of pages4
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume95
Issue number2
DOIs
StatePublished - Aug 2016

Fingerprint Dive into the research topics of 'Blood Group O-Dependent cellular responses to cholera toxin: Parallel clinical and epidemiological links to severe cholera'. Together they form a unique fingerprint.

Cite this