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dc.contributor.authorRickert, David M.
dc.contributor.authorHimmelberger, Riley
dc.contributor.authorCarbonetti, Nicholas H.
dc.contributor.authorScanlon, Karen
dc.contributor.authorSkerry, Ciaran
dc.date.accessioned2023-04-27T14:43:10Z
dc.date.available2023-04-27T14:43:10Z
dc.date.issued2023-03-31
dc.identifier.urihttp://hdl.handle.net/10713/20486
dc.descriptionPoster presented at SRC 2023, March 31, 2023.en_US
dc.description.abstractPertussis disease is associated with severe pulmonary inflammation and there is an urgent need to understand the mechanisms of pathogenesis to aid development of host-directed therapeutics. Bordetella pertussis produces a myriad of toxins to facilitate its pathogenesis, including tracheal cytotoxin (TCT), a monomeric fragment of peptidoglycan (PGN). We have identified the PGN recognition proteins (PGLYRP) and the host immune receptors, NOD1/2 as key players in the host response to infection. We hypothesized that TCT mediates pulmonary inflammatory pathology in mice and that therapeutic targeting of TCT may prevent this. To determine the contribution of TCT to host inflammatory responses, we infected mice with a mutant strain of B. pertussis which secretes excess TCT (TCT+). Mice challenged with TCT+ strain had increased pulmonary pathology supporting the idea that TCT drives pertussis pathogenesis. Further, we theorized TCT could be modulating inflammation via intracellular PGN sensors, NOD1 and NOD2, so we used cell reporter systems to determine if TCT stimulates responses via the NOD receptors. We characterized the interaction of TCT with human and mouse NOD1 and NOD2 and found TCT to be a potent stimulus mNOD1, implicating the receptor TCT-mediated pathogenesis. Previous work demonstrated PGLYRPs mediate host inflammatory responses to B. pertussis. To determine if PGLYRPs can modulate TCT-sensing by NOD receptors we used a HEK293-NOD reporter assay. PGLYRP1 and PGLYRP4 were found to increase NOD1 responses to TCT and decrease responses to NOD2. Together, these data reveal a novel mechanism through which inflammatory responses to B. pertussis TCT are determined.en_US
dc.language.isoen_USen_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectpeptidoglycan recognition proteinen_US
dc.subject.meshBordetella pertussis--immunologyen_US
dc.subject.meshCarrier Proteinsen_US
dc.subject.meshMiceen_US
dc.titleHost peptidoglycan recognition proteins and NOD receptors modulate the immune response to Bordetella pertussisen_US
dc.typePoster/Presentationen_US
refterms.dateFOA2023-04-27T14:43:11Z


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International