Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.

Intracellular Toll-like receptors (TLRs) expressed by dendritic cells recognize nucleic acids derived from pathogens and play an important role in the immune responses against the influenza virus (IAV), a single-stranded RNA sensed by different receptors including TLR7. However, the importance of TL...

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Autores principales:	Sophia Maschalidi, Signe Hässler, Fany Blanc, Fernando E Sepulveda, Mira Tohme, Michel Chignard, Peter van Endert, Mustapha Si-Tahar, Delphyne Descamps, Bénédicte Manoury
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/623955a6ac4443deb2789d13f0191415
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spelling	oai:doaj.org-article:623955a6ac4443deb2789d13f01914152021-11-18T06:04:05ZAsparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.1553-73661553-737410.1371/journal.ppat.1002841https://doaj.org/article/623955a6ac4443deb2789d13f01914152012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22916010/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Intracellular Toll-like receptors (TLRs) expressed by dendritic cells recognize nucleic acids derived from pathogens and play an important role in the immune responses against the influenza virus (IAV), a single-stranded RNA sensed by different receptors including TLR7. However, the importance of TLR7 processing in the development of anti-viral immune responses is not known. Here we report that asparagine endopeptidase (AEP) deficient mice are unable to generate a strong anti-IAV response, as demonstrated by reduced inflammation, cross presentation of cell-associated antigens and priming of CD8(+) T cells following TLR7-dependent pulmonary infection induced by IAV. Moreover, AEP deficient lung epithelial- or myeloid-cells exhibit impaired TLR7 signaling due to defective processing of this receptor. Indeed, TLR7 requires a proteolytic cleavage by AEP to generate a C-terminal fragment competent for signaling. Thus, AEP activity is critical for TLR7 processing, opening new possibilities for the treatment of influenza and TLR7-dependent inflammatory diseases.Sophia MaschalidiSigne HässlerFany BlancFernando E SepulvedaMira TohmeMichel ChignardPeter van EndertMustapha Si-TaharDelphyne DescampsBénédicte ManouryPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 8, p e1002841 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Sophia Maschalidi Signe Hässler Fany Blanc Fernando E Sepulveda Mira Tohme Michel Chignard Peter van Endert Mustapha Si-Tahar Delphyne Descamps Bénédicte Manoury Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
description	Intracellular Toll-like receptors (TLRs) expressed by dendritic cells recognize nucleic acids derived from pathogens and play an important role in the immune responses against the influenza virus (IAV), a single-stranded RNA sensed by different receptors including TLR7. However, the importance of TLR7 processing in the development of anti-viral immune responses is not known. Here we report that asparagine endopeptidase (AEP) deficient mice are unable to generate a strong anti-IAV response, as demonstrated by reduced inflammation, cross presentation of cell-associated antigens and priming of CD8(+) T cells following TLR7-dependent pulmonary infection induced by IAV. Moreover, AEP deficient lung epithelial- or myeloid-cells exhibit impaired TLR7 signaling due to defective processing of this receptor. Indeed, TLR7 requires a proteolytic cleavage by AEP to generate a C-terminal fragment competent for signaling. Thus, AEP activity is critical for TLR7 processing, opening new possibilities for the treatment of influenza and TLR7-dependent inflammatory diseases.
format	article
author	Sophia Maschalidi Signe Hässler Fany Blanc Fernando E Sepulveda Mira Tohme Michel Chignard Peter van Endert Mustapha Si-Tahar Delphyne Descamps Bénédicte Manoury
author_facet	Sophia Maschalidi Signe Hässler Fany Blanc Fernando E Sepulveda Mira Tohme Michel Chignard Peter van Endert Mustapha Si-Tahar Delphyne Descamps Bénédicte Manoury
author_sort	Sophia Maschalidi
title	Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
title_short	Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
title_full	Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
title_fullStr	Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
title_full_unstemmed	Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
title_sort	asparagine endopeptidase controls anti-influenza virus immune responses through tlr7 activation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/623955a6ac4443deb2789d13f0191415
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Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.

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