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

• Main Authors: Sophia Maschalidi, Signe Hässler, Fany Blanc, Fernando E Sepulveda, Mira Tohme, Michel Chignard, Peter van Endert, Mustapha Si-Tahar, Delphyne Descamps, Bénédicte Manoury
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2012-01-01
• Series: PLoS Pathogens
• Online Access: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22916010/pdf/?tool=EBI

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.