PMID- 20660347
OWN - NLM
STAT- MEDLINE
DCOM- 20100922
LR  - 20211020
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 185
IP  - 4
DP  - 2010 Aug 15
TI  - Mycobacterium tuberculosis and TLR2 agonists inhibit induction of type I IFN and 
      class I MHC antigen cross processing by TLR9.
PG  - 2405-15
LID - 10.4049/jimmunol.0904005 [doi]
AB  - Dendritic cells (DCs) cross process exogenous Ags and present them by class I MHC 
      (MHC-I) molecules to CD8(+) T cells specific for Ags from viruses and bacteria 
      such as Mycobacterium tuberculosis. Unmethylated CpG DNA signals through TLR9 to 
      induce type I IFN (IFN-alpha/beta), which enhances MHC-I Ag cross processing, but 
      lipoproteins that signal through TLR2 do not induce IFN-alpha/beta. In these 
      studies we observed that M. tuberculosis, which expresses agonists of both TLR9 
      and TLR2, did not induce production of IFN-alpha/beta or cross processing by 
      murine DCs. Furthermore, M. tuberculosis and TLR2 agonists inhibited induction of 
      IFN-alpha/beta and DC cross processing by CpG DNA. Exogenous IFN-alpha/beta 
      effectively enhanced cross processing of M. bovis bacillus Calmette-Guerin 
      expressing OVA, bypassing the inhibition of induction of endogenous 
      IFN-alpha/beta. In addition, inhibition of TLR9-induced cross processing of M. 
      bovis bacillus Calmette-Guerin expressing OVA could be circumvented by 
      pretreating cells with CpG DNA to induce IFN-alpha/beta and MHC-I cross 
      processing before inhibitory mycobacterial TLR2 agonists were present. Inhibition 
      of the response to one TLR by another may affect the ultimate response to 
      pathogens like M. tuberculosis that express agonists of multiple TLRs, including 
      TLR2 and TLR9. This mechanism may contribute to immune evasion and explain why 
      IFN-alpha/beta provides little contribution to host immunity to M. tuberculosis. 
      However, downregulation of certain TLR responses may benefit the host by 
      preventing detrimental excessive inflammation that may occur in the presence of 
      persistent infection.
FAU - Simmons, Daimon P
AU  - Simmons DP
AD  - Department of Pathology, Case Western Reserve University/University Hospitals 
      Case Medical Center, Cleveland, OH 44106, USA.
FAU - Canaday, David H
AU  - Canaday DH
FAU - Liu, Yi
AU  - Liu Y
FAU - Li, Qing
AU  - Li Q
FAU - Huang, Alex
AU  - Huang A
FAU - Boom, W Henry
AU  - Boom WH
FAU - Harding, Clifford V
AU  - Harding CV
LA  - eng
GR  - AI027243/AI/NIAID NIH HHS/United States
GR  - AI034343/AI/NIAID NIH HHS/United States
GR  - GM007250/GM/NIGMS NIH HHS/United States
GR  - HL055967/HL/NHLBI NIH HHS/United States
GR  - AI069085/AI/NIAID NIH HHS/United States
GR  - R01 AI035726/AI/NIAID NIH HHS/United States
GR  - AI077056/AI/NIAID NIH HHS/United States
GR  - R01 AI069085-05/AI/NIAID NIH HHS/United States
GR  - R01 AI034343-15S1/AI/NIAID NIH HHS/United States
GR  - R01 AI069085-04/AI/NIAID NIH HHS/United States
GR  - R01 AI069085/AI/NIAID NIH HHS/United States
GR  - R21 AI073217/AI/NIAID NIH HHS/United States
GR  - AI035726/AI/NIAID NIH HHS/United States
GR  - T32 GM007250/GM/NIGMS NIH HHS/United States
GR  - R01 AI034343-17/AI/NIAID NIH HHS/United States
GR  - R01 AI034343-15/AI/NIAID NIH HHS/United States
GR  - R01 AI035726-14/AI/NIAID NIH HHS/United States
GR  - R01 AI034343-16/AI/NIAID NIH HHS/United States
GR  - T32 HL083823/HL/NHLBI NIH HHS/United States
GR  - R01 AI035726-13/AI/NIAID NIH HHS/United States
GR  - HL083823/HL/NHLBI NIH HHS/United States
GR  - R01 AI069085-03/AI/NIAID NIH HHS/United States
GR  - AI073217/AI/NIAID NIH HHS/United States
GR  - R01 AI035726-15/AI/NIAID NIH HHS/United States
GR  - R01 AI034343/AI/NIAID NIH HHS/United States
GR  - R01 AI027243/AI/NIAID NIH HHS/United States
GR  - R01 HL055967/HL/NHLBI NIH HHS/United States
GR  - R21 AI077056/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100721
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (BCG Vaccine)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
RN  - 0 (Lipopeptides)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Pam(3)CSK(4) peptide)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr9 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 9)
RN  - 77238-31-4 (Interferon-beta)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - BCG Vaccine/immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - CpG Islands/genetics
MH  - Cross-Priming/drug effects/immunology
MH  - Dendritic Cells/drug effects/immunology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Interferon Type I/*immunology/metabolism/pharmacology
MH  - Interferon-alpha/immunology/metabolism/pharmacology
MH  - Interferon-beta/immunology/metabolism/pharmacology
MH  - Lipopeptides/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mycobacterium tuberculosis/genetics/*immunology
MH  - Oligodeoxyribonucleotides/pharmacology
MH  - Ovalbumin/immunology
MH  - Toll-Like Receptor 2/agonists/genetics/*immunology
MH  - Toll-Like Receptor 9/agonists/genetics/*immunology
PMC - PMC2990778
MID - NIHMS251797
COIS- Disclosures The authors have no financial conflicts of interest.
EDAT- 2010/07/28 06:00
MHDA- 2010/09/24 06:00
PMCR- 2011/08/15
CRDT- 2010/07/28 06:00
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2010/09/24 06:00 [medline]
PHST- 2011/08/15 00:00 [pmc-release]
AID - jimmunol.0904005 [pii]
AID - 10.4049/jimmunol.0904005 [doi]
PST - ppublish
SO  - J Immunol. 2010 Aug 15;185(4):2405-15. doi: 10.4049/jimmunol.0904005. Epub 2010 
      Jul 21.