The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites

Abstract

Sequestration of red blood cells infected with the human malaria parasite Plasmodium falciparum in organs such as the brain is considered important for pathogenicity. A similar phenomenon has been observed in mouse models of malaria, using the rodent parasite Plasmodium berghei, but it is unclear whether the P. falciparum proteins known to be involved in this process are conserved in the rodent parasite. Here we identify the P. berghei orthologues of two such key factors of P. falciparum, SBP1 and MAHRP1. Red blood cells infected with P. berghei parasites lacking SBP1 or MAHRP1a fail to bind the endothelial receptor CD36 and show reduced sequestration and virulence in mice. Complementation of the mutant P. berghei parasites with the respective P. falciparum SBP1 and MAHRP1 orthologues restores sequestration and virulence. These findings reveal evolutionary conservation of the machinery underlying sequestration of divergent malaria parasites and support the notion that the P. berghei rodent model is an adequate tool for research on malaria virulence.

Oxidative insult can induce malaria-protective trait of sickle and fetal erythrocytes

“…However, recent studies have shown that P. berghei -infected RBCs can sequester in different organs, including the brain5354, and that accumulation of parasitized RBCs, in addition to the recruitment and sequestration of activated CD8 + T cells55, is necessary for the development of cerebral malaria in mice56. Moreover, there is evidence of an evolutionary conserved machinery underlying sequestration and protein export to the host cell surface between P. berghei and P. falciparum species, although P. berghei lacks PfEMP1 adhesin orthologues57. Taking these findings into consideration, we explain the reduced brain damage in menadione-treated mice in light of our findings that menadione creates an oxidative imbalance in parasitized RBCs that interferes with the export and surface presentation of parasite-encoded virulence factors.…”

Toolbox for In Vivo Imaging of Host–Parasite Interactions at Multiple Scales

“…Intravital microscopy (IVM) is a powerful technique to investigate dynamic cellular processes and host-parasite interactions within functioning organs. Organs studied by IVM in the context of parasitology include the brain [1][2][3][4], the skin [5][6][7], the placenta [8,9], the lungs [10], the liver [11][12][13], and the spleen [14,15] (summarized in table 2, green=IVM exists; yellow=organ relevant but IVM never done; grey = IVM not done). Important advances in parasitology have been achieved using wide-field epifluorescence, confocal, spinning disc, or two-photon IVM.…”

Intravital imaging of host‐parasite interactions in organs of the thoracic and abdominopelvic cavities

“…(Image reproduced from Frevert, Nacer, Cabrera, Movila, & Leberl, ) (Scale bar, 50 μm). (ii) IVM still images showing the lungs of a UBC‐GFP mouse infected with WT PbANKA mCherry parasites displaying sequestration, and the lungs of a UBC‐GFP mouse infected with PbSBP1KO mCherry parasites (absent from the vasculature) (Image reproduced from De Niz et al, ) (Scale bar, 10 μm). (iii) An important biological finding in the field of Plasmodium was the egress of merozoites from liver‐derived merosomes in the pulmonary capillaries.…”

“…(Figure d(i)). A study using lung IVM in the context of Plasmodium aimed to study the dynamics of P. berghei relative to the vasculature when the machinery for protein export was intact, as opposed to when proteins PbMAHRP1a and PbSBP1 were absent (De Niz et al, ). P. falciparum MAHRP1 and SBP1 are known to be essential for virulence factor export and sequestration.…”