title: Influenza A virus infection of human primary dendritic cells impairs their ability to cross-present antigen to CD8 T cells.
abstract: Influenza A virus (IAV) infection is normally controlled by adaptive immune responses initiated by dendritic cells (DCs). We investigated the consequences of IAV infection of human primary DCs on their ability to function as antigen-presenting cells. IAV was internalized by both myeloid DCs (mDCs) and plasmacytoid DCs but only mDCs supported viral replication. Although infected mDCs efficiently presented endogenous IAV antigens on MHC class II, this was not the case for presentation on MHC class I. Indeed, cross-presentation by uninfected cells of minute amounts of endocytosed, exogenous IAV was -300-fold more efficient than presentation of IAV antigens synthesized by infected cells and resulted in a statistically significant increase in expansion of IAV-specific CD8 T cells. Furthermore, IAV infection also impaired cross-presentation of other exogenous antigens, indicating that IAV infection broadly attenuates presentation on MHC class I molecules. Our results suggest that cross-presentation by uninfected mDCs is a preferred mechanism of antigen-presentation for the activation and expansion of CD8 T cells during IAV infection.
authors.affiliation: Genentech, South San Francisco, California, USA. anna.smed.sorensen@ki.se
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.forename: Cécile
authors.initials: C
authors.lastname: Chalouni
authors.forename: Bithi
authors.initials: B
authors.lastname: Chatterjee
authors.forename: Lillian
authors.initials: L
authors.lastname: Cohn
authors.forename: Peter
authors.initials: P
authors.lastname: Blattmann
authors.forename: Norihiro
authors.initials: N
authors.lastname: Nakamura
authors.forename: Lélia
authors.initials: L
authors.lastname: Delamarre
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D053586:Virus Internalization
chemical_list: D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II