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Induction of apoptosis in host cells: a survival mechanism for Leishmania parasites?

Published online by Cambridge University Press:  08 September 2008

G. T. GETTI ,
R. A. CHEKE  and
D. P. HUMBER
G. T. GETTI*
Affiliation:
School of Health and Bioscience, University of East London, Stratford Campus, Romford Road, London E15 4LZ, UK Natural Resources Institute, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK
R. A. CHEKE
Affiliation:
Natural Resources Institute, University of Greenwich at Medway, Central Avenue, Chatham Maritime, Kent ME4 4TB, UK
D. P. HUMBER
Affiliation:
School of Health and Bioscience, University of East London, Stratford Campus, Romford Road, London E15 4LZ, UK
*
*Corresponding author: School of Health and Bioscience, University of East London, Stratford Campus, Romford Road, London E15 4LZ, UK. Tel: 020 82237305. E-mail: g.getti@uel.ac.uk
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Summary

Leishmania parasites invade host macrophages, causing infections that are either limited to skin or spread to internal organs. In this study, 3 species causing cutaneous leishmaniasis, L. major, L. aethiopica and L. tropica, were tested for their ability to interfere with apoptosis in host macrophages in 2 different lines of human monocyte-derived macrophages (cell lines THP-1 and U937) and the results confirmed in peripheral blood mononuclear cells (PBMC). All 3 species induced early apoptosis 48 h after infection (expression of phosphatidyl serine on the outer membrane). There were significant increases in the percentage of apoptotic cells both for U937 and PBMC following infection with each of the 3 species. Early apoptotic events were confirmed by mitochondrial membrane permeabilization detection and caspase activation 48 and 72 h after infection. Moreover, the percentage of infected THP-1 and U937 macrophages increased significantly (up to 100%) following treatment with an apoptosis inducer. Since phosphatidyl serine externalization on apoptosing cells acts as a signal for engulfment by macrophages, induction of apoptosis in the parasitized cells could actively participate in spreading the infection. In summary, parasite-containing apoptotic bodies with intact membranes could be released and phagocytosed by uninfected macrophages.

Keywords

LeishmaniaTHP-1U937infectionapoptosis
Type
Original Articles
Information
Parasitology , Volume 135 , Issue 12 , October 2008 , pp. 1391 - 1399
Copyright
Copyright © 2008 Cambridge University Press

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