CD36 and malaria: friends or foes? A decade of data provides some answers

Cabrera, Ana; Neculai, Dante; Kain, Kevin C.

doi:10.1016/j.pt.2014.07.006

Cited by 45 publications

(35 citation statements)

References 82 publications

(136 reference statements)

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“…While CD36 binders are predicted to be more common than EPCR binders, both parasite species have invested considerable genomic resources in retaining both adhesion traits. In addition to OxLDL and APC, a diverse array of ligands bind to CD36 and EPCR (60, 61). This suggests additional possible roles of CD36- and EPCR-based parasite adhesion in influencing a range of physiological and pathological processes which will be of interest to explore.…”

Section: Discussionmentioning

confidence: 99%

Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins

Brazier

Avril

Bernabeu

et al. 2017

mSphere

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Cytoadhesion of P. falciparum-infected erythrocytes in the microcirculation is a major virulence determinant. P. falciparum is descended from a subgenus of parasites that also infect chimpanzees and gorillas and exhibits strict host species specificity. Despite their high genetic similarity to P. falciparum, it is unknown whether ape parasites encode adhesion properties similar to those of P. falciparum or are as virulent in their natural hosts. Consequently, it has been unclear when virulent adhesion traits arose in P. falciparum and how long they have been present in the parasite population. It is also unknown whether cytoadhesive interactions pose a barrier to cross-species transmission. We show that parasite domains from the chimpanzee malaria parasite P. reichenowi bind human receptors with specificity similar to that of P. falciparum. Our findings suggest that parasite adhesion traits associated with both mild and severe malaria have much earlier origins than previously appreciated and have important implications for virulence evolution in a major human pathogen.

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Section: Discussionmentioning

confidence: 99%

Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins

Brazier

Avril

Bernabeu

et al. 2017

mSphere

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“…In addition to this, chimeric group B/A var genes encode EPCR-binding DBLα0-CIDRα1 head structures. The EPCR-binding phenotype has been implicated in severe malaria (18-21), whereas CD36 binding has been associated with uncomplicated malaria (22, 23). Severe malaria has been associated with rosetting, a phenomenon which involves binding between an IE and several uninfected erythrocytes but with unclear clinical significance.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of naturally acquired antibodies to PfEMP1 CIDR domain variants and their association with malaria protection

Obeng-Adjei

Larremore

Turner

et al. 2020

Preprint

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Malaria pathogenicity is determined, in part, by the adherence of Plasmodium falciparum infected erythrocytes to the microvasculature mediated via specific interactions between PfEMP1 variant domains to host endothelial receptors. Naturally acquired antibodies against specific PfEMP1 variants can play an important role in clinical protection against malaria. We evaluated IgG responses against a repertoire of PfEMP1 CIDR domain variants to determine the rate and order of variant-specific antibody acquisition and their association with protection against febrile malaria in a prospective cohort study conducted in an area of intense, seasonal malaria transmission. Using longitudinal data, we found that IgG to the pathogenic domain variants CIDRα1.7 and CIDRα1.8 were acquired the earliest. Furthermore, IgG to CIDRγ3 was associated with reduced prospective risk of febrile malaria and recurrent malaria episodes. Future studies will need to validate these findings in other transmission settings and determine the functional activity of these naturally acquired CIDR variant-specific antibodies.

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“…Importantly, expression of CD36 is low in the brain, even in the setting of cerebral malaria (Silamut et al, 1999), suggesting that binding to CD36 is most relevant in non-cerebral forms of severe malaria. CD36 is also believed to be an important macrophage pattern recognition receptor that mediates innate recognition and clearance of infected erythrocytes (Cabrera et al, 2014). Considering our current understanding, CD36 expression might be seen to contribute to malaria severity, by mediating cytoadherence, or to help control malaria, via immune effects.…”

Section: Introductionmentioning

confidence: 99%

Marked variation in prevalence of malaria-protective human genetic polymorphisms across Uganda

Walakira

Tukwasibwe

Kiggundu

et al. 2017

Infection, Genetics and Evolution

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A number of human genetic polymorphisms are prevalent in tropical populations and appear to offer protection against symptomatic and/or severe malaria. We compared the prevalence of four polymorphisms, the sickle hemoglobin mutation (β globin E6V), the α-thalassemia 3.7 kb deletion, glucose-6-phosphate dehydrogenase deficiency caused by the common African variant (G6PD A-), and the CD36 T188G mutation in 1,344 individuals residing in districts in eastern (Tororo), south-central (Jinja), and southwestern (Kanungu) Uganda. Genes of interest were amplified, amplicons subjected to mutation-specific restriction endonuclease digestion (for sickle hemoglobin, G6PD A-, and CD36 T188G), reaction products resolved by electrophoresis, and genotypes determined based on the sizes of reaction products. Mutant genotypes were common, with many more heterozygous than homozygous alleles identified. The prevalences (heterozygotes plus homozygotes) of sickle hemoglobin (28% Tororo, 25% Jinja, 7% Kanungu), α-thalassemia (53% Tororo, 45% Jinja, 18% Kanungu) and G6PD A- (29% Tororo, 18% Jinja, 8% Kanungu) were significantly greater in Tororo and Jinja compared to Kanungu (p<0.0001 for all three alleles); prevalences were also significantly greater in Tororo compared to Jinja for α-thalassemia (p = 0.03) and G6PD A- (p<0.0001). For the CD36 T188G mutation, the prevalence was significantly greater in Tororo compared to Jinja or Kanungu (27% Tororo, 17% Jinja, 18% Kanungu; p = 0.0004 and 0.0017, respectively). Considering ethnicity of study subjects, based on primary language spoken, the prevalence of mutant genotypes was lower in Bantu compared to non-Bantu language speakers, but in the Jinja cohort, the only study population with a marked diversity of language groups, prevalence did not differ between Bantu and non-Bantu speakers. These results indicate marked differences in human genetic features between populations in different regions of Uganda. These differences might be explained by both ethnic variation and by varied malaria risk in different regions of Uganda.

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CD36 and malaria: friends or foes? A decade of data provides some answers

Cited by 45 publications

References 82 publications

Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins

Pathogenicity Determinants of the Human Malaria Parasite Plasmodium falciparum Have Ancient Origins

Longitudinal analysis of naturally acquired antibodies to PfEMP1 CIDR domain variants and their association with malaria protection

Marked variation in prevalence of malaria-protective human genetic polymorphisms across Uganda

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