PMID- 20837474
OWN - NLM
STAT- MEDLINE
DCOM- 20110228
LR  - 20211020
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 47
DP  - 2010 Nov 19
TI  - Src homology 3-interacting domain of Rv1917c of Mycobacterium tuberculosis 
      induces selective maturation of human dendritic cells by regulating 
      PI3K-MAPK-NF-kappaB signaling and drives Th2 immune responses.
PG  - 36511-22
LID - 10.1074/jbc.M110.158055 [doi]
AB  - Mycobacterium tuberculosis, an etiological agent of pulmonary tuberculosis, 
      causes significant morbidity and mortality worldwide. Pathogenic mycobacteria 
      survive in the host by subverting host innate immunity. Dendritic cells (DCs) are 
      professional antigen-presenting cells that are vital for eliciting immune 
      responses to infectious agents, including pathogenic mycobacteria. DCs 
      orchestrate distinct Th responses based on the signals they receive. In this 
      perspective, deciphering the interactions of the proline-glutamic 
      acid/proline-proline-glutamic acid (PE/PPE) family of proteins of M. tuberculosis 
      with DCs assumes significant pathophysiological attributes. In this study, we 
      demonstrate that Rv1917c (PPE34), a representative member of the 
      proline-proline-glutamic-major polymorphic tandem repeat family, interacts with 
      TLR2 and triggers functional maturation of human DCs. Signaling perturbations 
      implicated a critical role for integrated cross-talk among PI3K-MAPK and NF-kappaB 
      signaling cascades in Rv1917c-induced maturation of DCs. However, this maturation 
      of DCs was associated with a secretion of high amounts of anti-inflammatory 
      cytokine IL-10, whereas Th1-polarizing cytokine IL-12 was not induced. Consistent 
      with these results, Rv1917c-matured DCs favored secretion of IL-4, IL-5, and 
      IL-10 from CD4(+) T cells and contributed to Th2-skewed cytokine balance ex vivo 
      in healthy individuals and in patients with pulmonary tuberculosis. 
      Interestingly, the Rv1917c-skewed Th2 immune response involved induced expression 
      of cyclooxygenase-2 (COX-2) in DCs. Taken together, these results indicate that 
      Rv1917c facilitates a shift in the ensuing immunity toward the Th2 phenotype and 
      could aid in immune evasion by mycobacteria.
FAU - Bansal, Kushagra
AU  - Bansal K
AD  - Department of Microbiology and Cell Biology, Indian Institute of Science, 
      Bangalore 560012, India.
FAU - Sinha, Akhauri Yash
AU  - Sinha AY
FAU - Ghorpade, Devram Sampat
AU  - Ghorpade DS
FAU - Togarsimalemath, Shambhuprasad Kotresh
AU  - Togarsimalemath SK
FAU - Patil, Shripad A
AU  - Patil SA
FAU - Kaveri, Srini V
AU  - Kaveri SV
FAU - Balaji, Kithiganahalli Narayanaswamy
AU  - Balaji KN
FAU - Bayry, Jagadeesh
AU  - Bayry J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100913
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rv1917c protein, Mycobacterium tuberculosis)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antigens, Bacterial/genetics/*metabolism
MH  - Bacterial Proteins/genetics/*metabolism
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cyclooxygenase 2/genetics/metabolism
MH  - Dendritic Cells/*immunology/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Signal-Regulated MAP Kinases/genetics/metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation
MH  - Humans
MH  - Mycobacterium tuberculosis/immunology/*metabolism
MH  - NF-kappa B/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes
MH  - Th2 Cells/*immunology/metabolism
MH  - Tuberculosis/immunology/*metabolism/microbiology
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
MH  - src Homology Domains
PMC - PMC2978579
EDAT- 2010/09/15 06:00
MHDA- 2011/03/01 06:00
PMCR- 2011/11/19
CRDT- 2010/09/15 06:00
PHST- 2010/09/15 06:00 [entrez]
PHST- 2010/09/15 06:00 [pubmed]
PHST- 2011/03/01 06:00 [medline]
PHST- 2011/11/19 00:00 [pmc-release]
AID - S0021-9258(20)46799-7 [pii]
AID - M110.158055 [pii]
AID - 10.1074/jbc.M110.158055 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Nov 19;285(47):36511-22. doi: 10.1074/jbc.M110.158055. Epub 
      2010 Sep 13.