Caspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesis

dc.contributor.authorCoutermarsh-Ott, Sherylen
dc.contributor.authorDoran, John T.en
dc.contributor.authorCampbell, Carolineen
dc.contributor.authorWilliams, Tere M.en
dc.contributor.authorLindsay, David S.en
dc.contributor.authorAllen, Irving C.en
dc.date.accessioned2017-03-26T19:19:56Zen
dc.date.available2017-03-26T19:19:56Zen
dc.date.issued2016-06-09en
dc.description.abstractToxoplasma gondii is an obligate intracellular parasite that is the etiologic agent responsible for toxoplasmosis. Infection with T. gondii results in activation of nucleotide binding domain and leucine rich repeat containing receptors (NLRs). NLR activation leads to inflammasome formation, the activation of caspase-1, and the subsequent cleavage of IL-1β and IL-18. Recently, a noncanonical inflammasome has been characterized which functions through caspase-11 and appears to augment many biological functions previously considered to be dependent upon the canonical inflammasome. To better elucidate the function of this noncanonical inflammasome in toxoplasmosis, we utilized Asc−/− and Casp11−/− mice and infected these animals with T. gondii. Our data indicates that caspase-11 modulates the innate immune response to T. gondii through a mechanism which is distinct from that currently described for the canonical inflammasome. Asc−/− mice demonstrated increased disease pathogenesis during the acute phase of T. gondii infection, whereas Casp11−/− mice demonstrated significantly attenuated disease pathogenesis and reduced inflammation. This attenuated host response was associated with reduced local and systemic cytokine production, including diminished IL-1β. During the chronic phase of infection, caspase-11 deficiency resulted in increased neuroinflammation and tissue cyst burden in the brain. Together, our data suggest that caspase-11 functions to protect the host by enhancing inflammation during the early phase of infection in an effort to minimize disease pathogenesis during later stages of toxoplasmosis.en
dc.description.versionPublished versionen
dc.format.extent? - ? (14) page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSheryl L. Coutermarsh-Ott, John T. Doran, Caroline Campbell, Tere M. Williams, David S. Lindsay, and Irving C. Allen, “Caspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesis,” Mediators of Inflammation, vol. 2016, Article ID 9848263, 14 pages, 2016. doi:10.1155/2016/9848263en
dc.identifier.doihttps://doi.org/10.1155/2016/9848263en
dc.identifier.issn0962-9351en
dc.identifier.orcidAllen, IC [0000-0001-9573-5250]en
dc.identifier.urihttp://hdl.handle.net/10919/76684en
dc.language.isoenen
dc.publisherHindawi Publishing Corpen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000378570900001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderCopyright © 2016 Sheryl L. Coutermarsh-Ott et al.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCell Biologyen
dc.subjectImmunologyen
dc.subjectDENDRITIC CELLSen
dc.subjectNLRP3 INFLAMMASOMEen
dc.subjectGAMMA-INTERFERONen
dc.subjectIMMUNE-RESPONSEen
dc.subjectINFECTIONen
dc.subjectACTIVATIONen
dc.subjectRECEPTORen
dc.subjectINNATEen
dc.subjectRESISTANCEen
dc.subjectMYD88en
dc.titleCaspase-11 Modulates Inflammation and Attenuates Toxoplasma gondii Pathogenesisen
dc.title.serialMediators of Inflammationen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen
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