Febrile temperature but not proinflammatory cytokines promotes phosphatidylserine expression on Plasmodium falciparum malaria‐infected red blood cells during parasite maturation

Abstract

Intraerythrocytic maturation of the malaria parasite Plasmodium falciparum is associated with profound changes in the asymmetry of phospholipids in the lipid bilayer of the parasitized red blood cells (pRBCs). These changes may contribute to adherence of pRBCs to endothelial cells. This study investigates the effect of febrile temperature and proinflammatory cytokines on phosphatidylserine (PS) expression on the exofacial surface of pRBCs during parasite maturation. The expression of PS on the pRBCs was determined by flow cytometry using fluorescein-labeled annexin V, which specifically binds to PS and a vital nucleic acid fluorochrome for parasite staining. The results showed that PS expression on the surface of pRBCs increased in association with parasite maturation, especially at the late parasite stage. Furthermore, the growth of P. falciparum also accelerated senescence of the uninfected RBCs in parasite cultures. Exposure to febrile temperature led to significant increases in the expression of PS on the surface of pRBCs, particularly at the late parasite stage associated with the virulence strain of the parasite. In contrast, proinflammatory cytokines had no detectable effect on PS expression on pRBCs. These data suggest that PS molecule expression is more dependent on fever, parasitemia, parasite strain, and virulence than on cytokine exposure. These findings contribute to our understanding of the factors that are involved in malaria pathogenesis.

Cytoadherence of erythrocytes invaded by Plasmodium falciparum: Quantitative contact-probing of a human malaria receptor

“…This behavior may be responsible for an overestimation of the b i values for the iRBC probes, which is also suggested by the average rupture forces determined strictly from single rupture event curves in the ranges presented in Table 2, i.e, 37 ± 1.9 pN (37°C) and 30 ± 1.6 pN (37°C/40°C(1h)) with p = 0.005, which compare, respectively, with b 1 = 43 pN at 37°C and b 1 = 34 pN at 37°C/40°C(1h) in Figures 4(b) and 5(c). Nonetheless, non-specific binding is expected to increase with febrile temperature exposure [40] and cannot justify the observed decrease in the single-molecule binding force (Δ b 1 in Table 1). …”

“…In this study, heating ring-stage iRBCs to 40 °C for 2 h enhanced the number of adherent cells and was associated with an increase in trafficking of Pf EMP1 to the cell surface.However, this effect seems absent in mature stages since the mean level of Pf EMP1 expression has not been altered by the transient exposure to 40 °C (Figure 6). On the other hand, febrile temperatures are known to promote phosphatidylserine expression on iRBCs membranes during parasite maturation [40]. This additional display of non–specific receptors may justify the increase in binding frequency observed for iRBC after exposure to febrile temperatures.…”

Evidencing the Role of Erythrocytic Apoptosis in Malarial Anemia

“…However, it was already reported that in P. falciparum in vitro cultures nRBCs are marked by PS externalization (Koka et al, 2007; Pattanapanyasat et al, 2010), and in our previous study with BALB/c mice infected by the lethal P. yoelii 17XL parasites, increased levels of nRBC apoptosis correlated with hiperparasitemia (Totino et al, 2013), indirectly suggesting that as do bacterial toxins (listeriolysin from Listeria monocytogenes and hemolysin from Vibrio parahaemolyticus ), peptidoglycan, and Schistosoma mansoni egg antigens (Lang et al, 2004b; Föller et al, 2007; Kasinathan and Greenberg, 2010; Jilani et al, 2012; Abed et al, 2013), plasmodial antigens can play a role in induction of erythrocytic apoptosis.…”

Turning up the heat: heat stress induces markers of programmed cell death in Plasmodium falciparum in vitro

“…In vitro studies have shown that P. falciparum growth rates and development were accelerated when parasites were exposed to 40 °C for 2 h, incubated at 37 °C for 10 h and again exposed to 40 °C for 12–24 h. 9 The parasite life cycle was also accelerated after exposure to less severe temperatures of 38.5–39 °C. 10 Incubation at 40 °C for 1–2 h enhanced the cytoadherence of mature P. falciparum -infected erythrocytes (pRBC) to CD36 and ICAM-1 receptors and also caused adherence of ring-stage parasites, which do not normally bind to these receptors. 11 Febrile temperatures have also been shown to reduce the deformability of pRBC, which may aid in sequestration, 12 as well inducing phosphatidylserine (PS) externalisation in pRBC.…”

“…11 Febrile temperatures have also been shown to reduce the deformability of pRBC, which may aid in sequestration, 12 as well inducing phosphatidylserine (PS) externalisation in pRBC. 10 …”