PMID- 15452235
OWN - NLM
STAT- MEDLINE
DCOM- 20041102
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 78
IP  - 20
DP  - 2004 Oct
TI  - Papillomavirus-like particles stimulate murine bone marrow-derived dendritic 
      cells to produce alpha interferon and Th1 immune responses via MyD88.
PG  - 11152-60
AB  - Dendritic cells (DCs) link innate and adaptive immunity by sensing pathogens or 
      vaccinogens and signaling a variety of defense responses. Since human 
      papillomavirus type 16 L1 virus-like particles (HPV16 VLPs) induce a potent, 
      protective immune response after vaccination, we examined their recognition by 
      DCs. HPV16 VLPs cause phenotypic maturation of murine bone marrow-derived DCs 
      (BMDCs), and immunization of mice with HPV16 VLP-loaded BMDCs or HPV16 VLPs alone 
      induced T helper 1 (Th1)-biased immune responses. Analysis of transcriptional 
      responses of murine BMDCs by microarray suggested that alpha/beta interferon 
      (IFN-alpha/beta) transcripts and numerous proinflammatory cytokines and 
      chemokines are up regulated in response to HPV16 VLPs. Indeed, the induction of 
      IFN-alpha, IFN-gamma, and interleukin-12 (IL-12) production by BMDCs after 
      stimulation with HPV16 VLPs was demonstrated by quantitative enzyme-linked 
      immunosorbent assay. Many microbial products that induce proinflammatory 
      responses are recognized via Toll-like receptor (TLR) signaling through the key 
      adaptor protein MyD88 and activation of NF-kappaB, nuclear factor of activated T 
      cells (NF-AT), and activating protein 1 (AP-1). Reporter assays indicated that 
      HPV16 VLPs activated NF-kappaB-, NF-AT-, and AP-1-dependent transcription in the 
      RAW264.7 macrophage cell line. Knockdown of MyD88 transcripts by small 
      interfering RNA in the RAW264.7 macrophage cell line inhibited the activation of 
      NF-kappaB-, NF-AT- and AP-1-dependent transcription by HPV16 VLP. Furthermore, 
      MyD88(-/-) BMDCs failed to up regulate IL-12 and IFN-alpha and -gamma in response 
      to HPV16 VLPs. Finally, Th1-biased immune responses to HPV16 VLPs are 
      dramatically impaired in MyD88 and IFN-alpha/beta receptor-deficient mice. This 
      implicates TLR recognition as central to immune recognition of HPV16 L1 VLPs.
FAU - Yang, Rongcun
AU  - Yang R
AD  - Department of Pathology, Johns Hopkins School of Medicine, Ross 512B, 720 Rutland 
      Avenue, Baltimore, MD 21205, USA.
FAU - Murillo, Francisco Martinez
AU  - Murillo FM
FAU - Cui, Hengmi
AU  - Cui H
FAU - Blosser, Richard
AU  - Blosser R
FAU - Uematsu, Satoshi
AU  - Uematsu S
FAU - Takeda, Kiyoshi
AU  - Takeda K
FAU - Akira, Shizuo
AU  - Akira S
FAU - Viscidi, Raphael P
AU  - Viscidi RP
FAU - Roden, Richard B S
AU  - Roden RB
LA  - eng
GR  - P01 AI048203/AI/NIAID NIH HHS/United States
GR  - P50 CA098252/CA/NCI NIH HHS/United States
GR  - P01 AI 48203/AI/NIAID NIH HHS/United States
GR  - P50 CA 098252/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Interferon-alpha)
RN  - 0 (MYD88 protein, human)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Receptors, Immunologic)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Antigens, Differentiation/genetics/*metabolism
MH  - Bone Marrow/immunology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Dendritic Cells/*immunology/metabolism/virology
MH  - Immunization
MH  - Interferon-alpha/*metabolism
MH  - Interferon-gamma/metabolism
MH  - Interleukin-12/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid Differentiation Factor 88
MH  - Papillomaviridae/*immunology/pathogenicity
MH  - Receptors, Immunologic/genetics/*metabolism
MH  - Th1 Cells/*immunology
MH  - Up-Regulation
MH  - Virion/*immunology
PMC - PMC521855
EDAT- 2004/09/29 05:00
MHDA- 2004/11/04 09:00
PMCR- 2004/10/01
CRDT- 2004/09/29 05:00
PHST- 2004/09/29 05:00 [pubmed]
PHST- 2004/11/04 09:00 [medline]
PHST- 2004/09/29 05:00 [entrez]
PHST- 2004/10/01 00:00 [pmc-release]
AID - 78/20/11152 [pii]
AID - 1145-04 [pii]
AID - 10.1128/JVI.78.20.11152-11160.2004 [doi]
PST - ppublish
SO  - J Virol. 2004 Oct;78(20):11152-60. doi: 10.1128/JVI.78.20.11152-11160.2004.