Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.

Detalhes bibliográficos
Autor(a) principal: Dotiwala, Farokh
Data de Publicação: 2016
Outros Autores: Mulik, Sachin, Barbosa, Rafael Polidoro Alves, Ansara, James A, Burleigh, Barbara A, Walch, Michael, Gazzinelli, Ricardo Tostes, Lieberman, Judy
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/14882
Resumo: 2018-07-14
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spelling Dotiwala, FarokhMulik, SachinBarbosa, Rafael Polidoro AlvesAnsara, James ABurleigh, Barbara AWalch, MichaelGazzinelli, Ricardo TostesLieberman, Judy2016-07-14T13:53:44Z2016-07-14T13:53:44Z2016DOTIWALA, Farokh et al. Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites. Nat Med., vol. 22, n. 2, p. 2010-216, 20161078-8956https://www.arca.fiocruz.br/handle/icict/1488210.1038/nm.4023engNature Publishing CompanyKiller lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article2018-07-14Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA/ Harvard Medical School. Department of Pediatrics. Boston, MA, USABoston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA/ Harvard Medical School. Department of Pediatrics. Boston, MA, USA.Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA/Harvard Medical School. Department of Pediatrics. Boston, MA, USA/ Fundação Oswaldo Cruz.Centro de Pesquisas René Rachou. Belo Horizonte, MG,Brasil.Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA.Harvard School of Public Health. Department of Immunology and Infectious Diseases. Boston, MA, USA.Université de Fribourg. Department of Medicine. Fribourg, Switzerland.Fundação Oswaldo Cruz.Centro de Pesquisas René Rachou. Belo Horizonte, MG,Brasil/ Harvard School of Public Health. Department of Immunology and Infectious Diseases. Boston, MA, USA/niversity of Massachusetts Medical School. Department of Medicine. Worcester, MA, USA.Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA/ Harvard Medical School. Department of Pediatrics. Boston, MA, USAProtozoan infections are a serious global health problem. Natural killer (NK) cells and cytolytic T lymphocytes (CTLs) eliminate pathogen-infected cells by releasing cytolytic granule contents--granzyme (Gzm) proteases and the pore-forming perforin (PFN)--into the infected cell. However, these cytotoxic molecules do not kill intracellular parasites. CD8(+) CTLs protect against parasite infections in mice primarily by secreting interferon (IFN)-γ. However, human, but not rodent, cytotoxic granules contain the antimicrobial peptide granulysin (GNLY), which selectively destroys cholesterol-poor microbial membranes, and GNLY, PFN and Gzms rapidly kill intracellular bacteria. Here we show that GNLY delivers Gzms into three protozoan parasites (Trypanosoma cruzi, Toxoplasma gondii and Leishmania major), in which the Gzms generate superoxide and inactivate oxidative defense enzymes to kill the parasite. PFN delivers GNLY and Gzms into infected cells, and GNLY then delivers Gzms to the intracellular parasites. Killer cell-mediated parasite death, which we term 'microbe-programmed cell death' or 'microptosis', is caspase independent but resembles mammalian apoptosis, causing mitochondrial swelling, transmembrane potential dissipation, membrane blebbing, phosphatidylserine exposure, DNA damage and chromatin condensation. GNLY-transgenic mice are protected against infection by T. cruzi and T. gondii, and survive infections that are lethal to wild-type mice. Thus, GNLY-, PFN- and Gzm-mediated elimination of intracellular protozoan parasites is an unappreciated immune defense mechanism.T-Lymphocyte/immunologyGranzymes/immunologyKiller Cells Natural/immunology LeishmaniasisCutaneous/immunologyMice TransgenicPerforin/immunologyT-LymphocytesToxoplasmosis/immunologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/14882/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALve_Farokh_Dotiwala_Killer_CPqRR_2016.pdfve_Farokh_Dotiwala_Killer_CPqRR_2016.pdfapplication/pdf2918329https://www.arca.fiocruz.br/bitstream/icict/14882/2/ve_Farokh_Dotiwala_Killer_CPqRR_2016.pdfd0fa33a58b48f2e5db8faf7a7b58e16cMD52TEXTve_Farokh_Dotiwala_Killer_CPqRR_2016.pdf.txtve_Farokh_Dotiwala_Killer_CPqRR_2016.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
title Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
spellingShingle Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
Dotiwala, Farokh
T-Lymphocyte/immunology
Granzymes/immunology
Killer Cells Natural/immunology Leishmaniasis
Cutaneous/immunology
Mice Transgenic
Perforin/immunology
T-Lymphocytes
Toxoplasmosis/immunology
title_short Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
title_full Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
title_fullStr Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
title_full_unstemmed Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
title_sort Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites.
author Dotiwala, Farokh
author_facet Dotiwala, Farokh
Mulik, Sachin
Barbosa, Rafael Polidoro Alves
Ansara, James A
Burleigh, Barbara A
Walch, Michael
Gazzinelli, Ricardo Tostes
Lieberman, Judy
author_role author
author2 Mulik, Sachin
Barbosa, Rafael Polidoro Alves
Ansara, James A
Burleigh, Barbara A
Walch, Michael
Gazzinelli, Ricardo Tostes
Lieberman, Judy
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Dotiwala, Farokh
Mulik, Sachin
Barbosa, Rafael Polidoro Alves
Ansara, James A
Burleigh, Barbara A
Walch, Michael
Gazzinelli, Ricardo Tostes
Lieberman, Judy
dc.subject.en.pt_BR.fl_str_mv T-Lymphocyte/immunology
Granzymes/immunology
Killer Cells Natural/immunology Leishmaniasis
Cutaneous/immunology
Mice Transgenic
Perforin/immunology
T-Lymphocytes
Toxoplasmosis/immunology
topic T-Lymphocyte/immunology
Granzymes/immunology
Killer Cells Natural/immunology Leishmaniasis
Cutaneous/immunology
Mice Transgenic
Perforin/immunology
T-Lymphocytes
Toxoplasmosis/immunology
description 2018-07-14
publishDate 2016
dc.date.accessioned.fl_str_mv 2016-07-14T13:53:44Z
dc.date.available.fl_str_mv 2016-07-14T13:53:44Z
dc.date.issued.fl_str_mv 2016
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv DOTIWALA, Farokh et al. Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites. Nat Med., vol. 22, n. 2, p. 2010-216, 2016
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/14882
dc.identifier.issn.pt_BR.fl_str_mv 1078-8956
dc.identifier.doi.none.fl_str_mv 10.1038/nm.4023
identifier_str_mv DOTIWALA, Farokh et al. Killer lymphocytes use granulysin, perforin and granzymes to kill intracellular parasites. Nat Med., vol. 22, n. 2, p. 2010-216, 2016
1078-8956
10.1038/nm.4023
url https://www.arca.fiocruz.br/handle/icict/14882
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Company
publisher.none.fl_str_mv Nature Publishing Company
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/14882/2/ve_Farokh_Dotiwala_Killer_CPqRR_2016.pdf
https://www.arca.fiocruz.br/bitstream/icict/14882/3/ve_Farokh_Dotiwala_Killer_CPqRR_2016.pdf.txt
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