Record Details

Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol

EPrints@IICB

View Archive Info
 
 
Field Value
 
Title Hyperlipidemia offers protection against Leishmania
donovani infection: role of membrane cholesterol
 
Creator Ghosh, June
Das, Shantanabha
Guha, Rajan
Ghosh, Debopam
Naskar, Kshudiram
Das, Anjan
Roy, Syamal
 
Subject Infectious Diseases and Immunology
 
Description Leishmania donovani (LD), the causative agent of
visceral leishmaniasis (VL), extracts membrane cholesterol
from macrophages and disrupts lipid rafts, leading to their
inability to stimulate T cells. Restoration of membrane cholesterol by liposomal delivery corrects the above defects
and offers protection in infected hamsters. To reinforce
further the protective role of cholesterol in VL, mice were
either provided a high-cholesterol (atherogenic) diet or underwent statin treatment. Subsequent LD infection showed
that an atherogenic diet is associated with protection, whereas hypocholesterolemia due to statin treatment confers susceptibility to the infection. This observation was validated in apolipoprotein E knockout mice (AE) mice that displayed intrinsic hypercholesterolemia with hepatic granuloma, production of host-protective cytokines, and expansion of antileishmanial CD8 + IFN- � + and CD8 + IFN- � + TNF- � + T cells in contrast to the wild-type C57BL/6 (BL/6) mice when infected with LD. Normal macrophages from AE mice (N-AEM) showed 3-fold higher membrane cholesterol coupled with increased fl uorescence anisotropy (FA) compared with wild-type macrophage (N-BL/6-M � ). Characterization of in vitro LD-infected AE macrophage (LD-AE-M � ) revealed intact raft architecture and ability to stimulate T cells, which were compromised in LD-BL/6-M � . This study clearly indicates that hypercholesterolemia, induced intrinsically or extrinsically, can control the pathogenesis of VL by modulating immune repertoire in favor of the host. —Ghosh, J., S.Das, R. Guha, D. Ghosh, K. Naskar, A. Das, and S. Roy. Hyperlipidemia offers protection against Leishmania donovani
infection: role of membrane cholesterol.
 
Publisher American Society for Biochemistry and Molecular Biology
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2271/1/JOURNAL_OF_LIPID_RESEARCH__V._53__(_12_)2560%2D2572;2012.pdf
Ghosh, June and Das, Shantanabha and Guha, Rajan and Ghosh, Debopam and Naskar, Kshudiram and Das, Anjan and Roy, Syamal (2012) Hyperlipidemia offers protection against Leishmania donovani infection: role of membrane cholesterol. Journal of Lipid Research, 53 (12). pp. 2560-2572.
 
Relation http://dx.doi.org/10.1194/jlr.M026914
http://www.eprints.iicb.res.in/2271/