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Clinical and Vaccine Immunology, June 2009, p. 889-898, Vol. 16, No. 6
1071-412X/09/$08.00+0 doi:10.1128/CVI.00453-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
9-O-Acetylated Sialoglycoproteins Are Important Immunomodulators in Indian Visceral Leishmaniasis 
Angana Ghoshal,1
Sumi Mukhopadhyay,1,2
Bibhuti Saha,2 and
Chitra Mandal1*
Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032,1 Department of Laboratory Medicine and Serology and Department of Tropical Medicine, School of Tropical Medicine, Kolkata 700073, India2
Received 2 December 2008/ Returned for modification 15 January 2009/ Accepted 22 April 2009
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-AcSA2-6GalNAc). 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.
* Corresponding author. Mailing address: Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India. Phone: 91-33-2429-8861. Fax: 91-33-2499-5717. E-mail: cmandal{at}iicb.res.in
Published ahead of print on 29 April 2009.
Clinical and Vaccine Immunology, June 2009, p. 889-898, Vol. 16, No. 6
1071-412X/09/$08.00+0 doi:10.1128/CVI.00453-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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