Dendritic cell aggresome-like-induced structure formation and delayed antigen presentation coincide in influenza virus-infected dendritic cells.
Influenza virus infection induces maturation of murine dendritic cells (DCs), which is most important for the initiation of an immune response. However, in contrast to EL-4 and MC57 cells, DCs present viral CTL epitopes with a delay of up to 10 h. This delay in Ag presentation coincides with the up-regulation of MHC class I molecules as well as costimulatory molecules on the cell surface and the accumulation of newly synthesized ubiquitinated proteins in large cytosolic structures, called DC aggresome-like-induced structures (DALIS). These structures were observed previously after LPS-induced maturation of DCs, and it was speculated that they play a role in the regulation of MHC class I Ag presentation. Our findings provide the first evidence for a connection between DC maturation, MHC class I-restricted Ag presentation, and DALIS formation, which is further supported by the observation that DALIS contain ubiquitinated influenza nucleoprotein.
Herter
Sylvia
S
Institute for Immunology, Johannes Gutenberg University of Mainz, Hochhaus am Augustusplatz, D-55131 Mainz, Germany.
Osterloh
Philipp
P
Hilf
Norbert
N
Rechtsteiner
Gerd
G
Höhfeld
Jörg
J
Rammensee
Hans-Georg
HG
Schild
Hansjörg
H
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D022083:Cytoplasmic Structures / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000821:virology; D013997:Time Factors; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D025801:Ubiquitin / Q000378:metabolism; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D025801:Ubiquitin; D014758:Viral Core Proteins