Role of Membrane Cholesterol in Leishmanial Infection
Leishmania is an obligate intracellular parasite that can invade and survive within host macrophages resulting in leishmaniasis, a major public health problem worldwide. The entry of intracellular parasites in general involves interaction with the plasma membrane of host cells. The molecular mechanisms involved in internalization of Leishmania are poorly characterized. Cholesterol in host cell membranes has recently been found to be necessary for binding and internalization of Leishmania. We propose that the reduction in leishmanial infection by cholesterol depletion/sequestration could be exploited to develop novel therapeutic strategies against leishmaniasis. This approach has the advantage of avoiding the commonly encountered drug resistance problem in tackling leishmaniasis.
KeywordsVisceral Leishmaniasis Membrane Cholesterol Cholesterol Depletion Host Macrophage Pathogen Entry
G-protein coupled receptor
Work in A.C.’s laboratory was supported by the Council of Scientific and Industrial Research, Govt. of India. A.C. is an Adjunct Professor at the Special Centre for Molecular Medicine of Jawaharlal Nehru University (New Delhi, India) and Indian Institute of Science Education and Research (Mohali, India), and Honorary Professor of the Jawaharlal Nehru Centre for Advanced Scientific Research (Bangalore, India). A.C. gratefully acknowledges J.C. Bose Fellowship (Dept. Science and Technology, Govt. of India). Some of the work described in this article was carried out by former members of A.C.’s group whose contributions are gratefully acknowledged. We gratefully acknowledge Sandeep Shrivastava for help in creating Figs. 14.1 and 14.2. We thank members of our laboratory for critically reading the manuscript.
- World Health Organization Website http://www.who.int/leishmaniasis/en/