Human papillomavirus type-16 virus-like particles activate complementary defense responses in key dendritic cell subpopulations.
Human papillomavirus type-16 (HPV16) L1 virus-like particles (VLPs) activate dendritic cells (DCs) and induce protective immunity. In this study, we demonstrate, using global gene expression analysis, that HPV16 VLPs produce quite distinct innate responses in murine splenic DC subpopulations. While HPV16 VLPs increase transcription of IFN-gamma and numerous Th1-related cytokines and chemokines in CD8alpha(+)CD11c(+) DCs, CD4(+)CD11c(+) DCs up-regulate only type I IFN and a different set of Th2-associated cytokines and chemokines. Type I IFN, but not IFN-gamma, potentiates humoral immunity, notably production of VLP-specific IgG2a. However, HPV16 VLP-stimulated IL-12 production by CD8alpha(+)CD11c(+) DCs is augmented by autocrine IFN-gamma signaling. Thus, before adaptive immunity, HPV16 VLPs signal complementary defense responses in key DC subpopulations, indicating specialized DC lineages with predetermined polarization.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rongcun
R
Yang
Francisco Martinez
FM
Murillo
Ken-Yu
KY
Lin
William H
WH
Yutzy
Satoshi
S
Uematsu
Kiyoshi
K
Takeda
Shizuo
S
Akira
Raphael P
RP
Viscidi
Richard B S
RB
Roden
D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020411:Oligonucleotide Array Sequence Analysis; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D016207:Cytokines; D009856:Oncogene Proteins, Viral