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The Journal of Immunology, 2004, 173: 2624-2631.
Copyright © 2004 by The American Association of Immunologists

Human Papillomavirus Type-16 Virus-Like Particles Activate Complementary Defense Responses in Key Dendritic Cell Subpopulations1

Rongcun Yang*, Francisco Martinez Murillo{dagger}, Ken-Yu Lin*, William H. Yutzy, IV*, Satoshi Uematsu, Kiyoshi Takeda, Shizuo Akira, Raphael P. Viscidi{ddagger} and Richard B. S. Roden2,*,§

Departments of * Pathology, {dagger} Molecular Biology and Genetics, {ddagger} Pediatrics, and § Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan

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 CD8{alpha}+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 CD8{alpha}+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.




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