Suicide for Survival - Death of Infected Erythrocytes as a Host Mechanism to Survive MalariaFöller M. · Bobbala D. · Koka S. · Huber S.M. · Gulbins E. · Lang F.
Departments of1Physiology and2Radiation Oncology, University of Tübingen,3Department of Molecular Biology, University of Duisburg-Essen
The pathogen of malaria, Plasmodium, enters erythrocytes and thus escapes recognition by the immune system. The pathogen induces oxidative stress to the host erythrocyte, which triggers eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are identified by macrophages which engulf and degrade the eryptotic cells. To the extent that infected erythrocytes undergo eryptosis prior to exit of Plasmodiaand subsequent infection of other erythrocytes, the premature eryptosis may protect against malaria. Accordingly, any therapeutical intervention accelerating suicidal death of infected erythrocytes has the potential to foster elimination of infected erythrocytes, delay the development of parasitemia and favorably influence the course of malaria. Eryptosis is stimulated by a wide variety of triggers including osmotic shock, oxidative stress, energy depletion and a wide variety of xenobiotics. Diseases associated with accelerated eryptosis include sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson’s disease. Among the known stimulators of eryptosis, paclitaxel, chlorpromazine, cyclosporine, curcumin, PGE2 and lead have indeed been shown to favourably influence the course of malaria. Moreover, sickle-cell trait, beta-thalassemia trait, glucose-6-phosphate dehydrogenase (G6PD)-deficiency and iron deficiency confer some protection against a severe course of malaria. Importantly, counteracting Plasmodia by inducing eryptosis is not expected to generate resistance of the pathogen, as the proteins involved in suicidal death of the host cell are not encoded by the pathogen and thus cannot be modified by mutations of its genes.
Prof. Dr. Florian Lang
Physiologisches Institut der Universität Tübingen
Gmelinstr. 5, D-72076 Tübingen (Germany)
Tel. +49 7071 29 72194, Fax: +49 7071 29 5618
Accepted: April 19, 2009
Published online: August 03, 2009
Number of Print Pages : 8
Cellular Physiology and Biochemistry (International Journal of Experimental Cellular Physiology, Biochemistry andPharmacology)
Vol. 24, No. 3-4, Year 2009 (Cover Date: 2009)
Journal Editor: F. Lang, Tübingen
ISSN: 1015–8987 (Print), eISSN: 1421–9778 (Online)
For additional information: http://www.karger.com/journals/cpb