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9-O-Acetylated Sialoglycoproteins Are Important Immunomodulators in Indian Visceral Leishmaniasis

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Title 9-O-Acetylated Sialoglycoproteins Are Important Immunomodulators
in Indian Visceral Leishmaniasis
 
Creator Ghoshal, Angana
Mukhopadhyay, Sumi
Saha, Bibhuti
Mandal, Chitra
 
Subject Infectious Diseases and Immunology
 
Description Overexpression of disease-associated 9-O-acetylated sialoglycoproteins (9-O-AcSGPs) on peripheral blood
mononuclear cells (PBMC) of visceral leishmaniasis (VL) patients (PBMCVL) compared to their levels of
expression in healthy individuals has been demonstrated using a lectin, achatinin-H, with specificity toward
9-O-acetylated sialic acid derivatives �2-6 linkage with subterminal N-acetylgalactosamine (9-O-AcSA�2-
6GalNAc). The decreased presence of disease-associated 9-O-AcSGPs on different immune cells of parasitologically
cured individuals after successful treatment relative to the levels in patients with active VL prior to
treatment was demonstrated. However, their contributory role as immunomodulatory determinants on PBMCVL
remained unexplored. Accordingly, 9-O-AcSGPs on PBMCVL were sensitized with achatinin-H, leading to
their enhanced proliferation compared to that observed with different known mitogens or parasite antigen.
This lymphoproliferative response was characterized by evaluation of the TH1/TH2 response by intracellular
staining and enzyme-linked immunosorbent assay for secreted cytokines, and the results were corroborated by
their genetic expression. Sensitized PBMCVL evidenced a mixed TH1/TH2 cellular response with a predominance
of the TH1 response, indicating the ability of 9-O-AcSGPs to modulate the host cell toward a favorable
response. Interestingly, the humoral and cellular responses showed a good correlation. Further, high levels of
anti-9-O-AcSGP antibodies with an order of distribution of immunoglobulin M (IgM) > IgG1 � IgG3 >
IgG4 > IgG2 > IgE could be explained by a mixed TH1/TH2 response. A good correlation of enhanced
9-O-AcSGPs with both the cell-mediated (r � 0.98) and humoral (r � 0.99) response was observed. In
summary, it may be concluded that sensitization of 9-O-AcSGPs on PBMCVL may provide a basis for the
modulation of the host’s immune response by their controlled expression, leading to a beneficial immune
response and influencing the disease pathology
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/144/1/CLINICAL_AND_VACCINE_IMMUNOLOGY%2C_16(_6)%2C_889%2D898%2C2009[66].pdf
Ghoshal, Angana and Mukhopadhyay, Sumi and Saha, Bibhuti and Mandal, Chitra (2009) 9-O-Acetylated Sialoglycoproteins Are Important Immunomodulators in Indian Visceral Leishmaniasis. Clinical and Vaccine Immunology, 16 (6). pp. 889-898.
 
Relation http://dx.doi.org/doi:10.1128/CVI.00453-08
http://www.eprints.iicb.res.in/144/