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Asparagine Endopeptidase Controls Anti-Influenza Virus Immune Responses through TLR7 Activation
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نویسنده
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maschalidi s. ,hässler s. ,blanc f. ,sepulveda f.e. ,tohme m. ,chignard m. ,van endert p. ,si-tahar m. ,descamps d. ,manoury b.
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منبع
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plos pathogens - 2012 - دوره : 8 - شماره : 8
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چکیده
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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. © 2012 maschalidi et al.
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آدرس
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inserm,unité 1013,paris,france,université paris descartes,sorbonne paris cité,faculté de médecine,paris, France, inserm,unité 1013,paris,france,université paris descartes,sorbonne paris cité,faculté de médecine,paris, France, unité de défense innée et inflammation,institut pasteur,paris,france,inserm,unité 874,paris, France, université paris descartes,sorbonne paris cité,faculté de médecine,paris,france,inserm,unité 768,paris, France, inserm,unité 1013,paris,france,université paris descartes,sorbonne paris cité,faculté de médecine,paris,france,inserm,unité 932,institut curie,paris, France, unité de défense innée et inflammation,institut pasteur,paris,france,inserm,unité 874,paris, France, inserm,unité 1013,paris,france,université paris descartes,sorbonne paris cité,faculté de médecine,paris, France, inserm,unité 1100,tours,france,faculté de médecine f. rabelais,tours, France, inserm,unité 1013,paris,france,université paris descartes,sorbonne paris cité,faculté de médecine,paris, France, inserm,unité 1013,paris,france,université paris descartes,sorbonne paris cité,faculté de médecine,paris, France
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Authors
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