Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation

Detalhes bibliográficos
Autor(a) principal: Mishra, Arun K.
Data de Publicação: 2012
Outros Autores: Alves, Joana E., Krumbach, Karin, Nigou, Jerome, Castro, António G., Geurtsen, Jeroen, Eggeling, Lothar, Saraiva, Margarida, Besra, Gurdyal S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/24249
Resumo: We acknowledge scientific discussions with Drs. Anne O'Garra, Luke Alderwick, and Apoorva Bhatt.
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spelling Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiationCytokineToll-like receptors (TLR)Dendritic cellsT cellGlycosyltransferasesScience & TechnologyWe acknowledge scientific discussions with Drs. Anne O'Garra, Luke Alderwick, and Apoorva Bhatt.Background: Lipoglycans modulate the initiation of immune responses by interacting with TLR2. Results: A hypermannosylated lipomannan variant, once recognized by the immune system, enhance both innate responses and Th17 differentiation. Conclusion: Altered lipoglycan structures are differently recognised by innate immune cells with an impact on the adaptive immune response. Significance: Specific lipoglycan structures may be useful to modulate immune responses. Resume: Toll-like receptors (TLRs) recognize pathogens by interacting with pathogen-associated molecular patterns, such as the phosphatidylinositol-based lipoglycans, lipomannan (LM) and lipoarabinomannan (LAM). Such structures are present in several pathogens, including Mycobacterium tuberculosis, being important for the initiation of immune responses. It is well established that the interaction of LM and LAM with TLR2 is a process dependent on the structure of the ligands. However, the implications of structural variations on TLR2 ligands for the development of T helper (Th) cell responses or in the context of in vivo responses are less studied. Herein, we used Corynebacterium glutamicum as a source of lipoglycan intermediates for host interaction studies. In this study, we have deleted a putative glycosyltransferase, NCgl2096, from C. glutamicum and found that it encodes for a novel α(1→2)arabinofuranosyltransferase, AftE. Biochemical analysis of the lipoglycans obtained in the presence (wild type) or absence of NCgl2096 showed that AftE is involved in the biosynthesis of singular arabinans of LAM. In its absence, the resulting molecule is a hypermannosylated (hLM) form of LAM. Both LAM and hLM were recognized by dendritic cells, mainly via TLR2, and triggered the production of several cytokines. hLM was a stronger stimulus for in vitro cytokine production and, as a result, a more potent inducer of Th17 responses. In vivo data confirmed hLM as a stronger inducer of cytokine responses and suggested the involvement of pattern recognition receptors other than TLR2 as sensors for lipoglycans.Margarida Saraiva Supported by Fundação para a Ciência e Tecnologia (FCT), Portugal, Personal Grant PTDC/SAU-MII/101977/2008; Gurdyal S. Besra Supported by a Personal Research Chair from James Bardrick, a Royal Society Wolfson Research Merit Award, a Lister Institute-Jenner research fellowship, the Medical Research Council, and Wellcome Trust Grant 081569/Z/06/Z. António G. Castro Supported by FCT, Portugal, Project Grant PTDC/SAU-MII/101977/2008. Jeroen Geurtsen Supported by the Netherlands Organization for Scientific Research (NWO) through a VENI research grant (016.101.001).American Society for Biochemistry and Molecular BiologyUniversidade do MinhoMishra, Arun K.Alves, Joana E.Krumbach, KarinNigou, JeromeCastro, António G.Geurtsen, JeroenEggeling, LotharSaraiva, MargaridaBesra, Gurdyal S.2012-112012-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/24249eng0021-925810.1074/jbc.M112.40239623144457http://www.jbc.org/content/287/53/44173.long#ack-1info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:29:32Zoai:repositorium.sdum.uminho.pt:1822/24249Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:24:32.711481Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
title Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
spellingShingle Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
Mishra, Arun K.
Cytokine
Toll-like receptors (TLR)
Dendritic cells
T cell
Glycosyltransferases
Science & Technology
title_short Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
title_full Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
title_fullStr Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
title_full_unstemmed Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
title_sort Differential arabinan capping of lipoarabinomannan modulates innate immune responses and impacts T helper cell differentiation
author Mishra, Arun K.
author_facet Mishra, Arun K.
Alves, Joana E.
Krumbach, Karin
Nigou, Jerome
Castro, António G.
Geurtsen, Jeroen
Eggeling, Lothar
Saraiva, Margarida
Besra, Gurdyal S.
author_role author
author2 Alves, Joana E.
Krumbach, Karin
Nigou, Jerome
Castro, António G.
Geurtsen, Jeroen
Eggeling, Lothar
Saraiva, Margarida
Besra, Gurdyal S.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Mishra, Arun K.
Alves, Joana E.
Krumbach, Karin
Nigou, Jerome
Castro, António G.
Geurtsen, Jeroen
Eggeling, Lothar
Saraiva, Margarida
Besra, Gurdyal S.
dc.subject.por.fl_str_mv Cytokine
Toll-like receptors (TLR)
Dendritic cells
T cell
Glycosyltransferases
Science & Technology
topic Cytokine
Toll-like receptors (TLR)
Dendritic cells
T cell
Glycosyltransferases
Science & Technology
description We acknowledge scientific discussions with Drs. Anne O'Garra, Luke Alderwick, and Apoorva Bhatt.
publishDate 2012
dc.date.none.fl_str_mv 2012-11
2012-11-01T00:00:00Z
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.uri.fl_str_mv http://hdl.handle.net/1822/24249
url http://hdl.handle.net/1822/24249
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-9258
10.1074/jbc.M112.402396
23144457
http://www.jbc.org/content/287/53/44173.long#ack-1
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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