Identification of a novel antigen-presenting cell population modulating antiinfluenza type 2 immunity.
Antiinfluenza type 2 (T2) immunity contributes to both immunopathology and immunoprotection, yet the underlying mechanisms modulating T2 immunity remain ill defined. We describe a novel mouse antigen (Ag)-presenting cell (APC), designated late-activator APC (LAPC). After pulmonary influenza A (H1N1) virus infection, LAPCs enter the lungs, capture viral Ag, and subsequently migrate to the draining lymph node (DLN) and spleen, with delayed kinetics relative to dendritic cells (DCs). In the DLN, influenza virus-activated LAPCs present Ag and selectively induce T helper type 2 (Th2) effector cell polarization by cell-cell contact-mediated modulation of GATA-3 expression. In adoptive transfer experiments, influenza virus-activated LAPCs augmented Th2 effector T cell responses in the DLN, increased production of circulating antiinfluenza immunoglobulin, and increased levels of T2 cytokines in bronchoalveolar lavage fluid in recipient influenza virus-infected mice. LAPC-recipient mice exhibited exacerbated pulmonary pathology, with delayed viral clearance and enhanced pulmonary eosinophilia. Collectively, our results identify and highlight the importance of LAPCs as immunomodulators of T2 immunity during influenza A virus infection.
Yoo
Jae-Kwang
JK
Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2M1, Canada.
Galligan
Carole L
CL
Virtanen
Carl
C
Fish
Eleanor N
EN
D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology* / Q000648:ultrastructure / Q000821:virology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002465:Cell Movement / Q000276:immunology; D016764:Cell Polarity / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology; D020869:Gene Expression Profiling; D007109:Immunity / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D010641:Phenotype; D021381:Protein Transport; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000821:virology
D000956:Antigens, Viral