Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay

Abstract

Apoptosis is the most common phenotype observed when cells die through programmed cell death. The morphologic and biochemical changes that characterize apoptotic cells depend on the activation of a diverse set of genes. Apoptosis is essential for multicellular organisms since their development and homeostasis are dependent on extensive cell renewal. In fact, there is strong evidence for the correlation between the emergence of multicellular organisms and apoptosis during evolution. On the other hand, no obvious advantages can be envisaged for unicellular organisms to carry the complex machinery required for programmed cell death. However, accumulating evidence shows that free-living and parasitic protozoa as well as yeasts display apoptotic markers. This phenomenon has been related to altruistic behavior, when a subpopulation of protozoa or yeasts dies by apoptosis, with clear benefits for the entire population. Recently, phosphatidylserine (PS) exposure and its recognition by a specific receptor (PSR) were implicated in the infectivity of amastigote forms of Leishmania, an obligatory vertebrate intramacrophagic parasite, showing for the first time that unicellular organisms use apoptotic features for the establishment and/or maintenance of infection. Here we focus on PS exposure in the outer leaflet of the plasma membrane -an early hallmark of apoptosis -and how it modulates the inflammatory activity of phagocytic cells. We also discuss the possible mechanisms by which PS exposure can define Leishmania survival inside host cells and the evolutionary implications of apoptosis at the unicellular level.

In Vitro and In Vivo Trypanocidal Effects of the Cyclopalladated Compound 7a, a Drug Candidate for Treatment of Chagas' Disease

“…The reason for this apoptosis-like process in a unicellular organism is still controversial. In parasites like Leishmania, it has been proposed that a few dead cells in the population stimulate infection (30). It has also been proposed that T. cruzi insect forms are killed by complement through extensive free radical production by the mitochondrion and induction of a similar apoptotic-like mechanism (12).…”

Hydrogen peroxide induces apoptosis-like death in Entamoeba histolytica trophozoites

“…Apoptosis is energy dependent and requires ATP for signalling from the cytoplasm to the nucleus of the cell. The physiological roles of the apoptosis in protozoa are unknown but this phenomenon is related to altruistic behaviour, with clear benefit for entire population or as a mechanism to avoid host death (Wanderley et al, 2005). H 2 O 2 , an important ROS, is a key mediator for eliciting PCD in mammalian and yeast cells (Li et al, 2000;Vollgraf et al, 1999;Clement & Pervaiz, 1999;Madeo et al, 1999).…”

Statins and Voriconazole Induce Programmed Cell Death in Acanthamoeba castellanii

“…These proteins are highly conserved cysteine proteases specific to aspartic acid (36). Other members of this family of proteins with homologous activities, such as paracaspases and metacaspases, have been commonly reported in unicellular organisms (37 (33,(38)(39)(40)(41). In these organisms, these apoptotic processes occur as a phenomenon that presumably benefits the rest of the population in some way.…”

“…In these organisms, these apoptotic processes occur as a phenomenon that presumably benefits the rest of the population in some way. Kin selection may limit the spread of amoebic parasites through colonies or under conditions where limited nutrients may mean the survival of some cells at the expense of others (33,(40)(41)(42) or cell damage, such as that induced by chemotherapy (41). The fact that there is evidence that apoptotic processes exist in protozoan parasites has provided new strategies for the development of tools in the study of these diseases, comparing these processes to the one in humans (42).…”