Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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.
Document type :
Journal articles
Complete list of metadata

Cited literature [44 references]  Display  Hide  Download

https://hal.inrae.fr/hal-02645446
Contributor : Migration Prodinra Connect in order to contact the contributor
Submitted on : Friday, May 29, 2020 - 1:42:08 AM
Last modification on : Thursday, October 7, 2021 - 2:24:06 PM

File

journal.ppat.1002841_1.PDF
Publisher files allowed on an open archive

Identifiers

Citation

Sophia Maschalidi, Signe Hässler, Fany Blanc, Fernando E. Sepulveda, Mira Tohmé, et al.. Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation. PLoS Pathogens, Public Library of Science, 2012, 8 (8), ⟨10.1371/journal.ppat.1002841⟩. ⟨hal-02645446⟩

Share

Metrics

Record views

81

Files downloads

202