In this study, we exploited these differences, combined with the recent crystal structure and 3-dimensional modeling of CD36, to investigate malaria-CD36 structure-function relationships and further define IE-CD36 binding interactions.
Here, to understand the function of CD36 in malaria immunity, we studied parasite growth, innate and adaptive immune responses, and host survival in WT and <i>Cd36</i><sup>-/-</sup> mice infected with a non-lethal strain of <i>Plasmodium yoelii</i> Compared with <i>Cd36</i><sup>-/-</sup> mice, WT mice had lower parasitemias and were resistant to death.
Importantly, CD36(+) monocytes/macrophages are also thought to participate in the tight control of the pro- and anti-inflammatory responses following Plasmodium detection through elimination of apoptotic cells and malaria-infected erythrocytes, internalization and recycling of oxidized forms of low-density lipoprotein and collaboration with TLR2 in pro-inflammatory response.
CM isolates bind significantly more to CD36 than to ICAM-1, which was correlated with high transcription level of group B var genes, supporting their implication in malaria pathogenesis.
In order to establish a link between cytoadherence, IRBC surface antibody recognition and the presence or absence of malaria symptoms, we phenotype-selected four Amazonian P. falciparum isolates and the laboratory strain 3D7 for their cytoadherence to CD36 and ICAM1 expressed on CHO cells.
Our results show that increased binding to CD36 is associated with uncomplicated malaria while ICAM-1 adhesion is raised in parasites from cerebral malaria cases.
We investigated the possible association of T188GCD36 gene polymorphism with severe clinical manifestations of malaria in 95 adult patients with severe malaria admitted to SCB Medical College Hospital, Cuttack, Orissa, India ('severe' group) and 95 ethnically matched controls attending outpatient clinics at primary health centres ('mild' group).
The protein also impacts survival to malaria and the influence of natural selection has resulted in high CD36 genetic variability in populations of African descent.
Association of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively).
CD36 is a broadly expressed membrane glycoprotein that acts as a facilitator of fatty acid uptake, a signaling molecule, and a receptor for a wide range of ligands, including apoptotic cells, modified forms of low density lipoprotein, thrombospondins, fibrillar beta-amyloid, components of Gram positive bacterial walls and malaria infected erythrocytes.
We replicated associations at HBB (P=.0008) and CD36 (P=.03) but also showed that the same variants are unusually differentiated in frequency between the Luo and Yoruba (who historically have been exposed to malaria) and the Masai and Kikuyu (who have not been exposed).
This article first presents an overview of published literature documenting the role of the scavenger receptor CD36 in activation of brain microglia with reference to brain pathologies such as Alzheimer's and malaria.
These observations suggest that the control of the TNF-alpha production in malaria by monocytes was not entirely dependent on the phagocytosis of PEs by CD36 and that soluble factors produced by PEs could play a role in this process.
We performed variation screening of the CD36 gene and examined the possible association between CD36 polymorphisms and the severity of malaria in 475 adult Thai patients with P. falciparum malaria.
For example, a specific phenotypic switch in adhesion from CD36 to chondroitin sulphate A (CSA) is associated with malaria pathogenesis in pregnant women.
These findings suggest that this Cd36 mutation might have a complex effect on malaria infection by decreasing parasite sequestration, and also by decreasing host immune responses.
The NL07 epitope appears to be functionally relevant and blocks CD36-mediated binding to red blood cells infected with the malaria parasite Plasmodium falciparum (IRBC).
RBCs from one African malaria patient were identified as deficient in CD36 and these RBCs did not rosette with the patient's own P falciparum PRBCs, even though these PRBCs were capable of rosetting with RBCs from a normal donor in a CD36-dependent manner.