PMID- 20404081
OWN - NLM
STAT- MEDLINE
DCOM- 20100709
LR  - 20211020
IS  - 1098-5522 (Electronic)
IS  - 0019-9567 (Print)
IS  - 0019-9567 (Linking)
VI  - 78
IP  - 7
DP  - 2010 Jul
TI  - The Lyme disease spirochete Borrelia burgdorferi utilizes multiple ligands, 
      including RNA, for interferon regulatory factor 3-dependent induction of type I 
      interferon-responsive genes.
PG  - 3144-53
LID - 10.1128/IAI.01070-09 [doi]
AB  - We recently discovered a critical role for type I interferon (IFN) in the 
      development of murine Lyme arthritis. Borrelia burgdorferi-mediated induction of 
      IFN-responsive genes by bone marrow-derived macrophages (BMDMs) was dependent 
      upon a functional type I IFN receptor but independent of Toll-like receptor 2 
      (TLR2), TLR4, TLR9, and the adapter molecule MyD88. We now demonstrate that 
      induction of the IFN transcriptional profile in B. burgdorferi-stimulated BMDMs 
      occurs independently of the adapter TRIF and of the cytoplasmic sensor NOD2. In 
      contrast, B. burgdorferi-induced transcription of these genes was dependent upon 
      a rapid STAT1 feedback amplification pathway. IFN profile gene transcription was 
      IRF3 dependent but did not utilize B. burgdorferi-derived DNA or DNase-sensitive 
      ligands. Instead, IFN-responsive gene expression could be induced by B. 
      burgdorferi-derived RNA. Interferon regulatory factor 3 (IRF3)-dependent IFN 
      profile gene transcription was also induced by sonicated bacteria, by the 
      lipoprotein OspA, and by factors released into the BSKII medium during culture of 
      B. burgdorferi. The IFN-stimulatory activity of B. burgdorferi culture 
      supernatants was not destroyed by nuclease treatment. Nuclease digestion also had 
      no effect on IFN profile induction mediated by sonicated B. burgdorferi. Thus, B. 
      burgdorferi-derived RNA, OspA, and non-nucleic acid ligands present in both 
      sonicated bacteria and B. burgdorferi culture medium contribute to type I 
      IFN-responsive gene induction. These findings suggest that B. burgdorferi 
      invasion of joint tissue and the resultant type I IFN induction associated with 
      Lyme arthritis development may involve multiple triggering ligands.
FAU - Miller, Jennifer C
AU  - Miller JC
AD  - Department of Pathology, University of Utah, Salt Lake City, Utah 84112, USA.
FAU - Maylor-Hagen, Heather
AU  - Maylor-Hagen H
FAU - Ma, Ying
AU  - Ma Y
FAU - Weis, John H
AU  - Weis JH
FAU - Weis, Janis J
AU  - Weis JJ
LA  - eng
GR  - R29 AI043521/AI/NIAID NIH HHS/United States
GR  - R01 AI024158/AI/NIAID NIH HHS/United States
GR  - AI-43521/AI/NIAID NIH HHS/United States
GR  - 5T32-AI055434/AI/NIAID NIH HHS/United States
GR  - AI-32223/AI/NIAID NIH HHS/United States
GR  - R56 AI032223/AI/NIAID NIH HHS/United States
GR  - AI-24158/AI/NIAID NIH HHS/United States
GR  - R01 AI032223/AI/NIAID NIH HHS/United States
GR  - R01 AR043521/AR/NIAMS NIH HHS/United States
GR  - T32 AI055434/AI/NIAID NIH HHS/United States
GR  - R01 AI043521/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100419
PL  - United States
TA  - Infect Immun
JT  - Infection and immunity
JID - 0246127
RN  - 0 (Interferon Regulatory Factor-3)
RN  - 0 (Interferon Type I)
RN  - 0 (Irf3 protein, mouse)
RN  - 0 (Nod2 Signaling Adaptor Protein)
RN  - 0 (Nod2 protein, mouse)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Borrelia burgdorferi/genetics/*physiology
MH  - Gene Expression Regulation, Bacterial/physiology
MH  - Genes, Bacterial/genetics/physiology
MH  - Interferon Regulatory Factor-3/*physiology
MH  - Interferon Type I/*biosynthesis/physiology
MH  - Lyme Disease/*microbiology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Nod2 Signaling Adaptor Protein/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT1 Transcription Factor/immunology/physiology
MH  - Transcription, Genetic/genetics/physiology
PMC - PMC2897372
EDAT- 2010/04/21 06:00
MHDA- 2010/07/10 06:00
PMCR- 2011/01/01
CRDT- 2010/04/21 06:00
PHST- 2010/04/21 06:00 [entrez]
PHST- 2010/04/21 06:00 [pubmed]
PHST- 2010/07/10 06:00 [medline]
PHST- 2011/01/01 00:00 [pmc-release]
AID - IAI.01070-09 [pii]
AID - 1070-09 [pii]
AID - 10.1128/IAI.01070-09 [doi]
PST - ppublish
SO  - Infect Immun. 2010 Jul;78(7):3144-53. doi: 10.1128/IAI.01070-09. Epub 2010 Apr 
      19.