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dc.contributor.authorAndrade, Warrison A.
dc.contributor.authorSouza, Maria do Carmo
dc.contributor.authorRamos-Martinez, Espiridion
dc.contributor.authorNagpal, Kamalpreet
dc.contributor.authorDutra, Miriam S.
dc.contributor.authorMelo, Mariane B.
dc.contributor.authorBartholomeu, Daniella C.
dc.contributor.authorGhosh, Sankar
dc.contributor.authorGolenbock, Douglas T.
dc.contributor.authorGazzinelli, Ricardo T.
dc.date2022-08-11T08:08:27.000
dc.date.accessioned2022-08-23T15:55:50Z
dc.date.available2022-08-23T15:55:50Z
dc.date.issued2013-01-16
dc.date.submitted2013-07-25
dc.identifier.citationCell Host Microbe. 2013 Jan 16;13(1):42-53. doi: 10.1016/j.chom.2012.12.003. <a href="http://dx.doi.org/10.1016/j.chom.2012.12.003">Link to article on publisher's site</a>
dc.identifier.issn1931-3128 (Linking)
dc.identifier.doi10.1016/j.chom.2012.12.003
dc.identifier.pmid23290966
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29843
dc.description.abstract"Triple-defective" (3d) mice carrying a mutation in UNC93B1, a chaperone for the endosomal nucleic acid-sensing (NAS) Toll-like receptors TLR3, TLR7, and TLR9, are highly susceptible to Toxoplasma gondii infection. However, none of the single or even the triple NAS-TLR-deficient animals recapitulated the 3d susceptible phenotype to experimental toxoplasmosis. Investigating this further, we found that while parasite RNA and DNA activate innate immune responses via TLR7 and TLR9, TLR11 and TLR12 working as heterodimers are required for sensing and responding to Toxoplasma profilin. Consequently, the triple TLR7/TLR9/TLR11-deficient mice are highly susceptible to T. gondii infection, recapitulating the phenotype of 3d mice. Humans lack functional TLR11 and TLR12 genes. Consistently, human cells produce high levels of proinflammatory cytokines in response to parasite-derived RNA and DNA, but not to Toxoplasma profilin, supporting a more critical role for NAS-TLRs in human toxoplasmosis.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23290966&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1016/j.chom.2012.12.003
dc.subjectImmunity
dc.subjectImmunology of Infectious Disease
dc.subjectMolecular Genetics
dc.subjectParasitic Diseases
dc.titleCombined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice
dc.typeJournal Article
dc.source.journaltitleCell host and microbe
dc.source.volume13
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/205
dc.identifier.contextkey4349482
html.description.abstract<p>"Triple-defective" (3d) mice carrying a mutation in UNC93B1, a chaperone for the endosomal nucleic acid-sensing (NAS) Toll-like receptors TLR3, TLR7, and TLR9, are highly susceptible to Toxoplasma gondii infection. However, none of the single or even the triple NAS-TLR-deficient animals recapitulated the 3d susceptible phenotype to experimental toxoplasmosis. Investigating this further, we found that while parasite RNA and DNA activate innate immune responses via TLR7 and TLR9, TLR11 and TLR12 working as heterodimers are required for sensing and responding to Toxoplasma profilin. Consequently, the triple TLR7/TLR9/TLR11-deficient mice are highly susceptible to T. gondii infection, recapitulating the phenotype of 3d mice. Humans lack functional TLR11 and TLR12 genes. Consistently, human cells produce high levels of proinflammatory cytokines in response to parasite-derived RNA and DNA, but not to Toxoplasma profilin, supporting a more critical role for NAS-TLRs in human toxoplasmosis.</p>
dc.identifier.submissionpathfaculty_pubs/205
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pages42-53


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