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Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells.

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells.
 
Creator Banerjee, Subha
Ghosh, June
Sen, Subha
Guha, Rajan
Dhar, Ranjan
Ghosh, Moumita
Datta, Sanchita
Raychaudhury, Bikramjit
Naskar, Kshudiram
Haldar, Arun Kumar
Lal, C.S
Pandey, K
Das, V. N. R
Das, Pradeep
 
Subject Infectious Diseases and Immunology
 
Description The membrane fluidity of antigen-presenting cells (APCs) has a significant bearing on T-cell-stimulating ability and is dependent on the cholesterol content of the membrane. The relationship, if any, between membrane fluidity and defective cell-mediated immunity in visceral leishmaniasis has been investigated. Systemic administration of cholesterol by liposome delivery (cholesterol liposomes) in Leishmania donovaniinfected hamsters was found to cure the infection. Splenic macrophages as a prototype of APCs in infected hamsters had decreased membrane cholesterol and an inability to drive T cells, which was corrected by cholesterol liposome treatment. The effect was cholesterol specific because liposomes made up of the analogue 4-cholesten-3-one provided almost no protection. Infection led to increases in interleukin-10 (IL-10), transforming growth factor beta, and IL-4 signals and concomitant decreases in gamma interferon (IFN-�), tumor necrosis factor alpha, and inducible NO synthase signals, which reverted upon cholesterol liposome treatment. The antileishmanial T-cell repertoire, whose expansion appeared to be associated with protection, was presumably type Th1, as shown by enhanced IFN-� signals and the predominance of the immunoglobulin G2 isotype. The protected group produced significantly more reactive oxygen species and NO than the infected groups, which culminated in killing of L. donovani parasites. Therefore, cholesterol liposome treatment may be yet another simple strategy to enhance the cell-mediated immune response to L. donovani infection. To our knowledge, this is the first report on the therapeutic effect of cholesterol liposomes in any form of the disease.
 
Publisher American Society for Microbiology
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/187/1/INFECTION_AND_IMMUNITY%2C77(6)%2C_2330%2D2342%2C2009[60].pdf
Banerjee, Subha and Ghosh, June and Sen, Subha and Guha, Rajan and Dhar, Ranjan and Ghosh, Moumita and Datta, Sanchita and Raychaudhury, Bikramjit and Naskar, Kshudiram and Haldar, Arun Kumar and Lal, C.S and Pandey, K and Das, V. N. R and Das, Pradeep (2009) Designing Therapies against Experimental Visceral Leishmaniasis by Modulating the Membrane Fluidity of Antigen-Presenting Cells. Infection and Immunity, 77 (6). pp. 2330-2342.
 
Relation http://dx.doi.org/10.1128/IAI.00057-09
http://www.eprints.iicb.res.in/187/