Unknown

Dataset Information

0

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.

SUBMITTER: Maschalidi S 

PROVIDER: S-EPMC3420946 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4467106 | biostudies-other
| S-EPMC5871875 | biostudies-literature
| S-EPMC5426628 | biostudies-literature
| S-EPMC3355091 | biostudies-literature
| S-EPMC7075946 | biostudies-literature
| S-EPMC8965739 | biostudies-literature
| S-EPMC5557514 | biostudies-other
| S-EPMC5871868 | biostudies-literature
2019-10-01 | GSE104806 | GEO
| S-EPMC3310399 | biostudies-literature