Regulation of intracellular Toll-like receptors signaling
Il 01/12/2017 ore 14.30 - 15.30
Sala Conferenze Area della Ricerca Na1, CNR Via P. Castellino, 111 80131 napoli
Dr. Bénédicte Manoury from the Institut Curie (Paris, France) will give a seminar about how intracellular TLR trafficking and signaling are regulated at the steady state and following bacterial and viral infection
The innate immune system provides the first barrier against pathogens. At the steady state, intracellular TLRs (TLR3, 7, 8 and 9) are retained in the endoplasmic reticulum together with a chaperone molecule, UNC93B1. Upon stimulation, they relocate to the endo/lysosomal compartment, thus allowing binding to their ligands and the recruitment of their adaptor molecules, MyD88 or TRIF. It has been shown that mouse TLR9 requires proteolytic cleavage in the endosomes to be functional. We are investigating which proteases regulate endosomal TLRs signaling and the role of these TLRs and chaperone molecules in the MHC class I antigen cross presentation pathway in dendritic cells. Manoury group's results indicate that AEP is a unique protease processing TLR7 and TLR9 in dendritic cells opening new therapeutical possibilities for the treatment of inflammatory and cancer diseases where TLR7 and 9 pathways are dysregulated.
1) Maschalidi S, Nunes-Hasler P, Nascimento C, Salent I, Lannoy V, Garfa-Traore M, Cagnard N, Sepulveda FE, Vargas P, Lennon-Duménil AM, van-Endert P, Capiod T, Demaurex N, Darasse-Jèze G, Manoury B. UNC93B1 interacts with the calcium sensor STIM1 for efficient antigen cross-presentation in dendritic cells. 2017 Nat. Commun. In press doi : 10.1038/s41467-017-01601-5
2) Babdor J, Descamps D, Adiko AC, Tohmé M, Maschalidi S, Evnouchidou I, Vasconcellos LR, De Luca M, Mauvais FX, Garfa-Traore M, Brinkmann MM, Chignard M, Manoury B, Saveanu L. IRAP+ endosomes restrict TLR9 activation and signaling. 2017 Nat. Immunol. May;18(5):509-518.
This article was chosen for the cover of Nature Immunology.
3) Maschalidi S, Hässler S, Blanc F, Sepulveda F, Tohme M, Chignard M, van Endert P, Si-Tahar M, Descamps D and Manoury B. Asparagine Endopeptidase Controls Anti-Influenza Virus Immune Responses through TLR7 Activation. 2012 PLOS Pathog.Aug;8(8):e1002841.
4) Descamps D, Le Gars M, Balloy V, Barbier D, Maschalidi S, Chignard M, Ramphal R, Manoury B, JM Sallenave. TLR5 activation, IL-1β signaling and asparagine endopeptidase activity: a new pathway for alveolar macrophage phagocytosis and bacterial killing. 2012 Proc Natl Acad Sci USA 109:1619-24.
5) Sepulveda F, Maschalidi S, Colisson R, Heslop L, sakka E, Ghirelli, C, Lennondumenil AM, Amigorena S, Cabanie L and Manoury B. Critical Role for Asparagine Endopeptidase in endocytic TLR signalling in dendritic cells. 2009 Immunity Nov 20, 31:731-748.
Piergiuseppe De Berardinis
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