Arabinosylated Lipoarabinomannan Skews Th2 Phenotype towards Th1 during Leishmania Infection by Chromatin Modification: Involvement of MAPK Signaling
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Arabinosylated Lipoarabinomannan Skews Th2
Phenotype towards Th1 during Leishmania Infection by
Chromatin Modification: Involvement of MAPK Signaling
|
|
| Creator |
Bhattacharya, Parna
Gupta, Gaurav Majumder, Saikat Adhikari, Anupam Banerjee, Sayantan Halder, Kuntal Bhattacharya Majumdar, Suchandra Ghosh, Moumita Chaudhuri, Shubho Roy, Syamal Majumdar, Subrata |
|
| Subject |
Infectious Diseases and Immunology
|
|
| Description |
The parasitic protozoan Leishmania donovani is the causative organism for visceral leishmaniasis (VL) which persists in the
host macrophages by deactivating its signaling machinery resulting in a critical shift from proinflammatory (Th1) to an antiinflammatory
(Th2) response. The severity of this disease is mainly determined by the production of IL-12 and IL-10 which
could be reversed by use of effective immunoprophylactics. In this study we have evaluated the potential of Arabinosylated
Lipoarabinomannan (Ara-LAM), a cell wall glycolipid isolated from non pathogenic Mycobacterium smegmatis, in regulating
the host effector response via effective regulation of mitogen-activated protein kinases (MAPK) signaling cascades in
Leishmania donovani infected macrophages isolated from BALB/C mice. Ara-LAM, a Toll-like receptor 2 (TLR2) specific ligand,
was found to activate p38 MAPK signaling along with subsequent abrogation of extracellular signal–regulated kinase (ERKs)
signaling. The use of pharmacological inhibitors of p38MAPK and ERK signaling showed the importance of these signaling
pathways in the regulation of IL-10 and IL-12 in Ara-LAM pretreated parasitized macrophages. Molecular characterization of
this regulation of IL-10 and IL-12 was revealed by chromatin immunoprecipitation assay (CHIP) which showed that in Ara-
LAM pretreated parasitized murine macrophages there was a significant induction of IL-12 by selective phosphorylation and
acetylation of histone H3 residues at its promoter region. While, IL-10 production was attenuated by Ara-LAM pretreatment
via abrogation of histone H3 phosphorylation and acetylation at its promoter region. This Ara-LAM mediated antagonistic
regulations in the induction of IL-10 and IL-12 genes were further correlated to changes in the transcriptional regulators
Signal transducer and activator of transcription 3 (STAT3) and Suppressor of cytokine signaling 3 (SOCS3). These results
demonstrate the crucial role played by Ara-LAM in regulating the MAPK signaling pathway along with subsequent changes
in host effector response during VL which might provide crucial clues in understanding the Ara-LAM mediated protection
during Leishmania induced pathogenesis.
|
|
| Date |
2011
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/1335/1/PLOS_ONE___6(_9)_____Article_Number_e24141;2011[37].pdf
Bhattacharya, Parna and Gupta, Gaurav and Majumder, Saikat and Adhikari, Anupam and Banerjee, Sayantan and Halder, Kuntal and Bhattacharya Majumdar, Suchandra and Ghosh, Moumita and Chaudhuri, Shubho and Roy, Syamal and Majumdar, Subrata (2011) Arabinosylated Lipoarabinomannan Skews Th2 Phenotype towards Th1 during Leishmania Infection by Chromatin Modification: Involvement of MAPK Signaling. PLoS ONE, 6 (9). |
|
| Relation |
http://dx.doi.org/10.1371/journal.pone.0024141
http://www.eprints.iicb.res.in/1335/ |
|