NKp46 and NKG2D recognition of infected dendritic cells is necessary for NK cell activation in the human response to influenza infection

Monia Draghi, Achal Pashine, Bharati Sanjanwala, Ketevan Gendzekhadze, Claudia Cantoni, David Cosman, Alessandro Moretta, Nicholas M. Valiante, Peter Parham

Research output: Contribution to journalArticlepeer-review

Abstract

At an early phase of viral infection, contact and cooperation between dendritic cells (DCs) and NK cells activates innate immunity, and also influences recruitment, when needed, of adaptive immunity. Influenza, an adaptable fast-evolving virus, anually causes acute, widespread infections that challenge the innate and adaptive immunity of humanity. In this study, we dissect and define the molecular mechanisms by which influenza-infected, human DCs activate resting, autologous NK cells. Three events in NK cell activation showed different requirements for soluble mediators made by infected DCs and for signals arising from contact with infected DCs. IFN-ai was mainly responsible for enhanced NK cytolysis and also important for CD69 up-regulation, whereas IL-12 was necessary for enhancing IFN-γ production. Increased CD69 expression and IFN-γ production, but not increased cytolysis, required recognition of influenza-infected DCs by two NK cell receptors: NKG2D and NKp46. Abs specific for these receptors or their known ligands (UL16-binding proteins 1-3 class I-like molecules for NKG2D and influenza hemagglutinin for NKp46) inhibited CD69 expression and IFN-γ production. Activation of NK cells by influenza-infected DCs and polyinosinic:polycytidylic acid (poly(I:C))-treated DCs was distinguished. Poly(I:C)-treated DCs did not express the UL16-binding protein 3 ligand for NKG2D, and in the absence of the influenza hemagglutinin there was no involvement of NKp46.

Original languageEnglish
Pages (from-to)2688-2698
Number of pages11
JournalJournal of Immunology
Volume178
Issue number5
Publication statusPublished - Mar 1 2007

ASJC Scopus subject areas

  • Immunology

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