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.
journal_name
PLoS Pathogjournal_title
PLoS pathogensauthors
Maschalidi S,Hässler S,Blanc F,Sepulveda FE,Tohme M,Chignard M,van Endert P,Si-Tahar M,Descamps D,Manoury Bdoi
10.1371/journal.ppat.1002841subject
Has Abstractpub_date
2012-01-01 00:00:00pages
e1002841issue
8eissn
1553-7366issn
1553-7374pii
PPATHOGENS-D-12-00678journal_volume
8pub_type
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