Reduction of pertussis inflammatory pathology by therapeutic treatment with sphingosine-1-phosphate receptor ligands by a pertussis toxin-Insensitive mechanism
JournalJournal of Infectious Diseases
PublisherOxford University Press
MetadataShow full item record
AbstractRecent data have demonstrated the potential of sphingosine 1-phosphate (S1P) receptor (S1PR) agonism in the treatment of infectious diseases. A previous study used a murine model of Bordetella pertussis infection to demonstrate that treatment with the S1PR agonist AAL-R reduces pulmonary inflammation during infection. In the current study, we showed that this effect is mediated via the S1PR1 on LysM+ (myeloid) cells. Signaling via this receptor results in reduced lung inflammation and cellular recruitment as well as reduced morbidity and mortality in a neonatal mouse model of disease. Despite the fact that S1PRs are pertussis toxin-sensitive G protein-coupled receptors, the effects of AAL-R were pertussis toxin insensitive in our model. Furthermore, our data demonstrate that S1PR agonist administration may be effective at therapeutic time points. These results indicate a role for S1P signaling in B. pertussis-mediated pathology and highlight the possibility of host-Targeted therapy for pertussis. Copyright The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
SponsorsThis work was supported by the National Institute of Allergy and Infectious Diseases (Public Health Service grants AI-119566 and AI-117095.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85021857586&doi=10.1093%2finfdis%2fjiw536&partnerID=40&md5=6249f1bb0136e3f2d27d3db8c5ceee88; http://hdl.handle.net/10713/9882