Plasmodium falciparum infection-induced changes in erythrocyte membrane proteins

Abstract

Over the past decade, advances in proteomic and mass spectrometry techniques and the sequencing of the Plasmodium falciparum genome have led to an increasing number of studies regarding the parasite proteome. However, these studies have focused principally on parasite protein expression, neglecting parasite-induced variations in the host proteome. Here, we investigated P. falciparum-induced modifications of the infected red blood cell (iRBC) membrane proteome, taking into account both host and parasite proteome alterations. Furthermore, we also determined if some protein changes were associated with genotypically distinct P. falciparum strains. Comparison of host membrane proteomes between iRBCs and uninfected red blood cells using fluorescence-based proteomic approaches, such as 2D difference gel electrophoresis revealed that more than 100 protein spots were highly up-represented (fold change increase greater than five) following P. falciparum infection for both strains (i.e. RP8 and Institut Pasteur Pregnancy Associated Malaria). The majority of spots identified by mass spectrometry corresponded to Homo sapiens proteins. However, infection-induced changes in host proteins did not appear to affect molecules located at the outer surface of the plasma membrane. The under-representation of parasite proteins could not be attributed to deficient parasite protein expression. Thus, this study describes for the first time that considerable host protein modifications were detected following P. falciparum infection at the erythrocyte membrane level. Further analysis of infection-induced host protein modifications will improve our knowledge of malaria pathogenesis.

Protective vaccination and blood-stage malaria modify DNA methylation of gene promoters in the liver of Balb/c mice

“…The vaccine consists of host cell plasma membranes, isolated in the form of ghosts from P. chabaudi-parasitized red blood cells as described elsewhere (Wunderlich et al 1985. These ghosts contain parasite-synthesized proteins (Wunderlich et al 1988b, c), as it has been also described for plasma membranes of P. falciparum-infected erythrocytes (Fontaine et al 2012). Approximately 10 6 ghosts suspended in 100 μl Freund's complete adjuvant were injected twice on week 3 and week 1 before challenging with 10 6 P. chabaudiparasitized red blood cells (Krücken et al 2009).…”

Liver-inherent immune system: its role in blood-stage malaria

“…In accordance, it has been recently found that autoantibodies and sera from patients suffering from diverse autoimmune conditions, but not from malaria, inhibit the in vitro growth of P. falciparum in human RBCs (Bhatnagar et al, 2011; Brahimi et al, 2011). Especially that type of autoimmunity is apparently required for protection against blood-stage malaria (Daniel-Ribeiro, 2000), that is presumably directed against autoantigens and parasite-induced neo-autoantigens on the surface of Plasmodium -infected RBCs (Wunderlich et al, 1988b,c; Fontaine et al, 2012). It is therefore not surprising that surface membranes of Plasmodium -infected RBCs can be used for protective vaccination of malaria-susceptible mice, which raises their survival from 0 to more than 80% and decreases peak parasitemia by about 30% (Wunderlich et al, 1988a; Krücken et al, 2009).…”

Differential miRNA Expression in the Liver of Balb/c Mice Protected by Vaccination during Crisis of Plasmodium chabaudi Blood-Stage Malaria

“…Moreover, there is a vaccination technique available by which survival of mice, being naturally susceptible to malaria, can be raised from 0% to over 80% (Wunderlich et al, 1988a; Krücken et al, 2009). This technique, which uses a non-infectious vaccine consisting of surface membranes isolated from P. chabaudi -infected erythrocytes containing parasite-synthesized proteins (Wunderlich et al, 1988b,c; Fontaine et al, 2012), converts lethal blood-stage infections to take a self-healing course (Krücken et al, 2009). Upon challenging with 10 6 P. chabaudi -parasitized erythrocytes, all non-vaccinated mice succumb to malaria during the crisis phase of infection, whereas the majority of vaccinated mice survive the infections and generate long-lasting immune mechanisms against homologous re-challenge (Krücken et al, 2009).…”