UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii

Detalhes bibliográficos
Autor(a) principal: Melo, Mariane B.
Data de Publicação: 2010
Outros Autores: Kasperkovitz, Pia, Cerny, Anna, Konen Waisman, Stephanie, Jones, Evelyn A. Kurt, Lien, Egil, Beutler, Bruce, Howard, Jonathan C., Golenbock, Douglas Taylor, Gazzinelli, Ricardo Tostes
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/5878
Resumo: National Institutes of Health, National Institute of Science and Technology for Vaccines/CNPq
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spelling Melo, Mariane B.Kasperkovitz, PiaCerny, AnnaKonen Waisman, StephanieJones, Evelyn A. KurtLien, EgilBeutler, BruceHoward, Jonathan C.Golenbock, Douglas TaylorGazzinelli, Ricardo Tostes2012-11-27T15:33:08Z2012-11-27T15:33:08Z2010MELO, Mariane B, et al. (2010) UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii. PLoS Pathog 6(8): e1001071.15537366https://www.arca.fiocruz.br/handle/icict/587810.1371/journal.ppat.1001071National Institutes of Health, National Institute of Science and Technology for Vaccines/CNPqUniversity of Massachusetts Medical School. Worcester, MA, United States of AmericaUniversity of Massachusetts Medical School. Worcester, MA, United States of AmericaUniversity of Massachusetts Medical School. Worcester, MA, United States of AmericaInstitute for Genetics, University of Cologne. Cologne, GermanyUniversity of Massachusetts Medical School. Worcester, MA, United States of AmericaUniversity of Massachusetts Medical School. Worcester, MA, United States of AmericaScripps Research Institute. La Jolla, CA, United States of AmericaInstitute for Genetics, University of Cologne. Cologne, GermanyUniversity of Massachusetts Medical School. Worcester, MA, United States of America/ Fundacão Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, BrazilUniversity of Massachusetts Medical School. Worcester, MA, United States of America , Fundacão Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Belo Horizonte, MG, BrazilUNC93B1 associates with Toll-Like Receptor (TLR) 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFa and IFNc, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wildtype and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNc by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in nonactivated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNc production as well as autonomous control of Toxoplasma replication by macrophages.engPublic Library of Science (PLoS)UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondiiinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleToxoplasma gondiiResistance to Infectioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINAL81.2010.pdf81.2010.pdfapplication/pdf3661304https://www.arca.fiocruz.br/bitstream/icict/5878/1/81.2010.pdf252043c16fd200ff3cab0fcfb011853bMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82008https://www.arca.fiocruz.br/bitstream/icict/5878/2/license.txt06db3f0df647fd9ddff657403bbe0ee2MD52TEXT81.2010.pdf.txt81.2010.pdf.txtExtracted texttext/plain73908https://www.arca.fiocruz.br/bitstream/icict/5878/5/81.2010.pdf.txtbb661d4d9b44a032ff842cce0c107e8cMD55THUMBNAIL81.2010.pdf.jpg81.2010.pdf.jpgGenerated Thumbnailimage/jpeg2269https://www.arca.fiocruz.br/bitstream/icict/5878/4/81.2010.pdf.jpgb45c40149b35477522a59615d42e9730MD54icict/58782018-04-25 12:47:06.743oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352018-04-25T15:47:06Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
title UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
spellingShingle UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
Melo, Mariane B.
Toxoplasma gondii
Resistance to Infection
title_short UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
title_full UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
title_fullStr UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
title_full_unstemmed UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
title_sort UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii
author Melo, Mariane B.
author_facet Melo, Mariane B.
Kasperkovitz, Pia
Cerny, Anna
Konen Waisman, Stephanie
Jones, Evelyn A. Kurt
Lien, Egil
Beutler, Bruce
Howard, Jonathan C.
Golenbock, Douglas Taylor
Gazzinelli, Ricardo Tostes
author_role author
author2 Kasperkovitz, Pia
Cerny, Anna
Konen Waisman, Stephanie
Jones, Evelyn A. Kurt
Lien, Egil
Beutler, Bruce
Howard, Jonathan C.
Golenbock, Douglas Taylor
Gazzinelli, Ricardo Tostes
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Melo, Mariane B.
Kasperkovitz, Pia
Cerny, Anna
Konen Waisman, Stephanie
Jones, Evelyn A. Kurt
Lien, Egil
Beutler, Bruce
Howard, Jonathan C.
Golenbock, Douglas Taylor
Gazzinelli, Ricardo Tostes
dc.subject.en.pt_BR.fl_str_mv Toxoplasma gondii
Resistance to Infection
topic Toxoplasma gondii
Resistance to Infection
description National Institutes of Health, National Institute of Science and Technology for Vaccines/CNPq
publishDate 2010
dc.date.issued.fl_str_mv 2010
dc.date.accessioned.fl_str_mv 2012-11-27T15:33:08Z
dc.date.available.fl_str_mv 2012-11-27T15:33:08Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.citation.fl_str_mv MELO, Mariane B, et al. (2010) UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii. PLoS Pathog 6(8): e1001071.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/5878
dc.identifier.issn.none.fl_str_mv 15537366
dc.identifier.doi.none.fl_str_mv 10.1371/journal.ppat.1001071
identifier_str_mv MELO, Mariane B, et al. (2010) UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii. PLoS Pathog 6(8): e1001071.
15537366
10.1371/journal.ppat.1001071
url https://www.arca.fiocruz.br/handle/icict/5878
dc.language.iso.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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