Journal
CHEMISTRY AND PHYSICS OF LIPIDS
Volume 199, Issue -, Pages 179-185Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.chemphyslip.2016.02.007
Keywords
CARC; CRAC; Host-pathogen interaction; Leishmania; Membrane cholesterol; Mycobacterium
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Funding
- Council of Scientific and Industrial Research (Govt. of India) Network project [BSC0114]
- J.C. Bose Fellowship from the Department of Science and Technology, Govt. of India
- Council of Scientific and Industrial Research
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The cellular plasma membrane serves as a portal for the entry of intracellular pathogens. An essential step for an intracellular pathogen to gain entry into a host cell therefore is to be able to cross the cell membrane. In this review, we highlight the role of host membrane cholesterol in regulating the entry of intracellular pathogens using insights obtained from work on the interaction of Leishmania and Mycobacterium with host cells. The entry of these pathogens is known to be dependent on host membrane cholesterol. Importantly, pathogen entry is inhibited either upon depletion (or complexation), or enrichment of membrane cholesterol. In other words, an optimum level of host membrane cholesterol is necessary for efficient infection by pathogens. In this overall context, we propose a general mechanism, based on cholesterol-induced conformational changes, involving cholesterol binding sites in host cell surface receptors that are implicated in this process. A therapeutic strategy targeting modulation of membrane cholesterol would have the advantage of avoiding the commonly encountered problem of drug resistance in tackling infection by intracellular pathogens. Insights into the role of host membrane cholesterol in pathogen entry would be instrumental in the development of novel therapeutic strategies to effectively tackle intracellular pathogenesis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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