PMID- 16785544
OWN - NLM
STAT- MEDLINE
DCOM- 20060809
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 177
IP  - 1
DP  - 2006 Jul 1
TI  - Impaired generation of reactive oxygen species during differentiation of 
      dendritic cells (DCs) by Mycobacterium tuberculosis secretory antigen (MTSA) and 
      subsequent activation of MTSA-DCs by mycobacteria results in increased 
      intracellular survival.
PG  - 468-78
AB  - We investigated the role of reactive oxygen species (ROS) in dendritic cell (DC) 
      differentiation by 10-kDa Mycobacterium tuberculosis secretory Ag (MTSA) and 
      survival of mycobacteria therein. Compared with GM-CSF, MTSA induced lower ROS 
      production during DC differentiation from precursors. This result correlated with 
      higher superoxide dismutase 1 expression in MTSA stimulated precursors as 
      compared with GM-CSF stimulation. Furthermore, a negative regulation of protein 
      kinase C (PKC) activation by ROS was observed during DC differentiation. ROS 
      inhibited the rapid and increased phosphorylation of PKCalpha observed during DC 
      differentiation by MTSA. In contrast, ROS inhibition increased the weak and 
      delayed PKCalpha phosphorylation by GM-CSF. Similar to DC differentiation, upon 
      activation with either M. tuberculosis cell extract (CE) or live Mycobacterium 
      bovis bacillus Calmette-Guerin (BCG), DCs differentiated with MTSA (MTSA-DCs) 
      generated lower ROS levels when compared with DCs differentiated with GM-CSF 
      (GM-CSF-DCs). Likewise, a negative regulation of PKCalpha phosphorylation by ROS 
      was once again observed in DCs activated with either M. tuberculosis CE or live 
      M. bovis BCG. However, a reciprocal positive regulation between ROS and calcium 
      was observed. Compared with MTSA-DCs, stimulation of GM-CSF-DCs with M. 
      tuberculosis CE induced a 2-fold higher ROS-dependent calcium influx. However, 
      pretreatment of MTSA-DCs with H(2)O(2) increased calcium mobilization. Finally, 
      lower ROS levels in MTSA-DCs correlated with increased intracellular survival of 
      M. bovis BCG when compared with survival in GM-CSF-DCs. Although inhibiting ROS 
      in GM-CSF-DCs increased M. bovis BCG survival, H(2)O(2) treatment of MTSA-DCs 
      decreased survival of M. bovis BCG. Overall our results suggest that DCs 
      differentiated with Ags such as MTSA may provide a niche for survival and/or 
      growth of mycobacteria following sequestration of ROS.
FAU - Sinha, Aprajita
AU  - Sinha A
AD  - Immunology Group, International Centre for Genetic Engineering and Biotechnology, 
      Aruna Asaf Ali Marg, New Delhi 110067, India.
FAU - Singh, Anjana
AU  - Singh A
FAU - Satchidanandam, Vijaya
AU  - Satchidanandam V
FAU - Natarajan, Krishnamurthy
AU  - Natarajan K
LA  - eng
GR  - AI 75320/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Bacterial Proteins)
RN  - 0 (CFP-10 protein, Mycobacterium tuberculosis)
RN  - 0 (Reactive Oxygen Species)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Bacterial Proteins/*physiology
MH  - Calcium Signaling/immunology
MH  - Cell Differentiation/*immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/enzymology/immunology/*metabolism/*microbiology
MH  - Down-Regulation/immunology
MH  - Female
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/physiology
MH  - Intracellular Fluid/enzymology/immunology/*microbiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mycobacterium bovis/immunology
MH  - Mycobacterium tuberculosis/*growth & development/immunology/pathogenicity
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Reactive Oxygen Species/*antagonists & inhibitors/immunology/metabolism
MH  - Superoxide Dismutase/physiology
MH  - Superoxide Dismutase-1
MH  - Up-Regulation/immunology
EDAT- 2006/06/21 09:00
MHDA- 2006/08/10 09:00
CRDT- 2006/06/21 09:00
PHST- 2006/06/21 09:00 [pubmed]
PHST- 2006/08/10 09:00 [medline]
PHST- 2006/06/21 09:00 [entrez]
AID - 177/1/468 [pii]
AID - 10.4049/jimmunol.177.1.468 [doi]
PST - ppublish
SO  - J Immunol. 2006 Jul 1;177(1):468-78. doi: 10.4049/jimmunol.177.1.468.