PMID- 25223368
OWN - NLM
STAT- MEDLINE
DCOM- 20150708
LR  - 20231213
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 26
IP  - 12
DP  - 2014 Dec
TI  - Mycobacterium tuberculosis promotes Th17 expansion via regulation of human 
      dendritic cells toward a high CD14 and low IL-12p70 phenotype that reprograms 
      upon exogenous IFN-gamma.
PG  - 705-16
LID - 10.1093/intimm/dxu085 [doi]
AB  - The capacity to develop protective immunity against mycobacteria is 
      heterogeneously distributed among human beings, and it is currently unknown why 
      the initial immune response induced against Mycobacterium tuberculosis (Mtb) does 
      not provide proper clearance of this pathogen. Dendritic cells (DCs) are some of 
      the first cells to interact with Mtb and they play an essential role in 
      development of protective immunity against Mtb. Given that Mtb-infected 
      macrophages have difficulties in degrading Mtb, they need help from 
      IFN-gamma-producing CD4+ T cells propagated via IL-12p70-producing DCs. Here we 
      report that Mtb modifies human DC plasticity by expanding a CD14+ DC subset with 
      weak IL-12p70-producing capacity. The CD14+ Mtb-promoted subset was furthermore 
      poor inducers of IFN-gamma by naive CD4+ T cells, but instead prompted 
      IL-17A-producing RORgammaT+ CD4+ T cells. Mtb-derived peptidoglycan and mannosylated 
      lipoarabinomannan partly recapitulated the subset partition induced by Mtb. 
      Addition of IFN-gamma, but neither IL-17A nor IL-22, which are potentially produced 
      by Mtb-exposed gamma/delta-T cells in mucosal linings, inhibited the differentiation 
      toward CD14+ DCs and promoted high-level IL-12p70 in Mtb-challenged DCs. We 
      conclude that Mtb exploits DC plasticity to reduce production of IL-12p70, and 
      that this process is entirely divertible by exogenous IFN-gamma. These data suggest 
      that strategies to increase local IFN-gamma production in the lungs of tuberculosis 
      patients may boost host immunity toward Mtb.
CI  - (c) The Japanese Society for Immunology. 2014. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Sondergaard, Jonas Norskov
AU  - Sondergaard JN
AD  - Center for Biological Sequence Analysis, Department of Systems Biology, Technical 
      University of Denmark, DK-2800 Kgs. Lyngby, Denmark Present address: Nijmegen 
      Centre for Molecular Life Sciences, Department of Tumor Immunology, Radboud 
      University Nijmegen Medical Centre, Nijmegen, The Netherlands.
FAU - Laursen, Janne Marie
AU  - Laursen JM
AD  - Center for Biological Sequence Analysis, Department of Systems Biology, Technical 
      University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
FAU - Rosholm, Lisbeth Buus
AU  - Rosholm LB
AD  - Center for Biological Sequence Analysis, Department of Systems Biology, Technical 
      University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
FAU - Brix, Susanne
AU  - Brix S
AD  - Center for Biological Sequence Analysis, Department of Systems Biology, Technical 
      University of Denmark, DK-2800 Kgs. Lyngby, Denmark sbp@bio.dtu.dk.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140915
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Antigens, Surface)
RN  - 0 (Interleukin-17)
RN  - 0 (Interleukins)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - 0 (Peptidoglycan)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Antigens, Surface/metabolism
MH  - Dendritic Cells/drug effects/*immunology/*metabolism
MH  - Humans
MH  - Immunophenotyping
MH  - Interferon-gamma/pharmacology
MH  - Interleukin-12/*metabolism
MH  - Interleukin-17/pharmacology
MH  - Interleukins/pharmacology
MH  - Lipopolysaccharide Receptors/*metabolism
MH  - Mycobacterium tuberculosis/immunology
MH  - Peptidoglycan/immunology/pharmacology
MH  - Phenotype
MH  - T-Lymphocyte Subsets/drug effects/immunology/metabolism
MH  - Th1 Cells/immunology/metabolism
MH  - Th17 Cells/drug effects/*immunology/*metabolism
MH  - Tuberculosis/*immunology/*metabolism
MH  - Interleukin-22
OTO - NOTNLM
OT  - IL-17
OT  - co-stimulatory molecules
OT  - mannosylated lipoarabinomannan
OT  - monocytes
OT  - naive CD4 T cells
EDAT- 2014/09/17 06:00
MHDA- 2015/07/15 06:00
CRDT- 2014/09/17 06:00
PHST- 2014/09/17 06:00 [entrez]
PHST- 2014/09/17 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
AID - dxu085 [pii]
AID - 10.1093/intimm/dxu085 [doi]
PST - ppublish
SO  - Int Immunol. 2014 Dec;26(12):705-16. doi: 10.1093/intimm/dxu085. Epub 2014 Sep 
      15.