Dataset Information

Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria.

ABSTRACT: In Plasmodium falciparum malaria, CD8+ T cells play a double-edged role. Liver-stage specific CD8+ T cells can confer protection, as has been shown in several vaccine studies. Blood-stage specific CD8+ T cells, on the other hand, contribute to the development of cerebral malaria in murine models of malaria. The role of CD8+ T cells in humans during the blood-stage of P. falciparum remains unclear. As part of a cross-sectional malaria study in Ghana, granzyme B levels and CD8+ T cells phenotypes were compared in the peripheral blood of children with complicated malaria, uncomplicated malaria, afebrile but asymptomatically infected children and non-infected children. Granzyme B levels in the plasma were significantly higher in children with febrile malaria than in afebrile children. CD8+ T cells were the main T cell subset expressing granzyme B. The proportion of granzyme B+ CD8+ T cells was significantly higher in children with complicated malaria than in uncomplicated malaria, whereas the activation marker CD38 on CD8+ T cells showed similar expression levels. This suggests a pathogenic role of cytotoxic CD8+ T cells in the development of malaria complications in humans.

SUBMITTER: Kaminski LC

PROVIDER: S-EPMC6918797 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria.

Kaminski Lea-Christina LC Riehn Mathias M Abel Annemieke A Steeg Christiane C Yar Denis Dekugmen DD Addai-Mensah Otchere O Aminkiah Francis F Owusu Dabo Ellis E Jacobs Thomas T Mackroth Maria Sophia MS

Frontiers in immunology 20191211

In Plasmodium falciparum malaria, CD8+ T cells play a double-edged role. Liver-stage specific CD8+ T cells can confer protection, as has been shown in several vaccine studies. Blood-stage specific CD8+ T cells, on the other hand, contribute to the development of cerebral malaria in murine models of malaria. The role of CD8+ T cells in humans during the blood-stage of P. falciparum remains unclear. As part of a cross-sectional malaria stud ...[more]

PMID: 31921176

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Project description:BACKGROUND: Plasmodium falciparum exports proteins that remodel the erythrocyte membrane. One such protein, called Pf155/RESA (RESA1) contributes to parasite fitness, optimizing parasite survival during febrile episodes. Resa1 gene is a member of a small family comprising three highly related genes. Preliminary evidence led to a search for clues indicating the involvement of RESA2 protein in the pathophysiology of malaria. In the present study, cDNA sequence of resa2 gene was obtained from two different strains. The proportion of P. falciparum isolates having a non-stop T1526C mutation in resa2 gene was evaluated and the association of this genotype with severity of malaria was investigated. METHODS: Resa2 cDNAs of two different strains (a patient isolate and K1 culture adapted strain) was obtained by RT-PCR and DNA sequencing was performed to confirm its gene structure. The proportion of isolates having a T1526C mutation was evaluated using a PCR-RFLP methodology on groups of severe malaria and uncomplicated patients recruited in 1991-1994 in Senegal and in 2009 in Benin. RESULTS: A unique ORF with an internal translation stop was found in the patient isolate (Genbank access number : JN183870), while the K1 strain harboured the T1526C mutation (Genbank access number : JN183869) which affects the internal stop codon and restores a full length coding sequence. About 14% of isolates obtained from Senegal and Benin harboured mutant T1526C parasites. Some isolates had both wild and mutant resa alleles. The analysis excluding those mixed isolates showed that the resa2 T1526C mutation was found more frequently in severe malaria cases than in uncomplicated cases (p?=?0.008). The association of the presence of the mutant allele and parasitaemia >4% was shown in multivariate analysis (p?=?0.03) in the group of Beninese children. CONCLUSIONS: All T1526C mutant parasites theoretically have the ability to give rise to a full-length RESA2 protein. This study raises the hypothesis that the RESA2 protein could favour high-density infections. Other studies in various geographic settings and probably including more patients are now required to replicate these results and to answer the questions raised by these results.

Dataset Information

Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe Plasmodium Falciparum Malaria.

Publications

Cytotoxic T Cell-Derived Granzyme B Is Increased in Severe <i>Plasmodium Falciparum</i> Malaria.

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