Dichotomous miR expression and immune responses following primary blood-stage malaria

Burel, Julie G.; Apte, Simon H.; Groves, Penny; Boyle, Michelle J.; Langer, Christine; Beeson, James G.; McCarthy, James S.; Doolan, Denise L.

doi:10.1172/jci.insight.93434

Cited by 32 publications

(25 citation statements)

References 44 publications

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“…Tregs have an established role in suppressing effector immune responses to a variety of pathogens, including malarial parasites [ 22 , 23 ]. CD69 expression in CD4+ T cells has been shown to correlate with the development of antigen-specific antibodies in experimental human falciparum malaria [ 24 ]. CD69 is a transmembrane glycoprotein expressed during early activation and increases with inflammation with the potential to induce cytotoxic activity once crosslinked [ 25 – 29 ], whereas CD25 (IL-2α receptor) has been associated with T cell proliferation and differentiation through the IL-2 cytokine [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection

Frimpong

Kusi

Tornyigah

et al. 2018

Malar J

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BackgroundAsymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear.MethodsIn a cross-sectional study, the levels of Tregs and other T cell activation phenotypes were compared using flow cytometry in symptomatic, asymptomatic and uninfected children before and after stimulation with infected red blood cell lysates (iRBCs). In addition, the association between these T cell phenotypes and parasitaemia were investigated.ResultsIn children with asymptomatic infections, levels of Tregs and activated T cells were comparable to those in healthy controls but significantly lower than those in symptomatic children. After iRBC stimulation, levels of Tregs remained lower for asymptomatic versus symptomatic children. In contrast, levels of activated T cells were higher for asymptomatic children. Strikingly, the pre-stimulation levels of two T cell activation phenotypes (CD8+CD69+ and CD8+CD25+CD69+) and the post-stimulation levels of two regulatory phenotypes (CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+) were significantly positively correlated with and explained 68% of the individual variation in parasitaemia. A machine-learning model based on levels of these four phenotypes accurately distinguished between asymptomatic and symptomatic children (sensitivity = 86%, specificity = 94%), suggesting that these phenotypes govern the observed variation in disease status.ConclusionCompared to symptomatic P. falciparum infections, in children asymptomatic infections are characterized by lower levels of Tregs and activated T cells, which are associated with lower parasitaemia. The results indicate that T cell regulatory and activation phenotypes govern both parasitaemia and disease status in paediatric malaria in the studied sub-Saharan African population.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2410-6) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection

Frimpong

Kusi

Tornyigah

et al. 2018

Malar J

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“…Single-nucleotide polymorphisms of microRNA influence the biogenesis of microRNA and subsequently affect both the expression level of mature microRNA and target recognition. (Jazdzewski et al, 2008) During malaria disease, a differential expression of microRNA has been demonstrated in Anopheles mosquitos (Prapansilp & Turner, 2013), the brain tissue of mice with CM (El-Assaad et al, 2011;Matin-Alonso et al, 2018), the postmortem kidney tissue from humans (Prapansilp & Turner, 2013), and plasma from malaria patients compared to the respective nonmalarial controls (Chamnanchanunt, Fucharoen, & Umemura, 2017;Chamnanchanunt et al, 2015). These findings highlight the hypothesis that microRNA SNPs have a potential role in the severity of malaria disease (i.e., whether cerebral or not).…”

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confidence: 82%

microRNA‐27a and microRNA‐146aSNPin cerebral malaria

Wah

Hananantachai

Patarapotikul

et al. 2019

Molec Gen & Gen Med

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Background During Plasmodium falciparum infection, micro RNA expression alters in brain tissue of mice with cerebral malaria compared to noninfected controls. Micro RNA regulates gene expression post‐transcriptionally to influence biological processes. Cerebral malaria pathology caused mainly by the immunological disorder. We hypothesize that single‐nucleotide polymorphism in a micro RNA influences micro RNA biogenesis or target gene recognition and altering susceptibility to cerebral malaria. Methods We performed a literature search based on immunological mechanism and applied micro RNA ‐related single‐nucleotide polymorphisms database to examine candidate micro RNA SNP s possibly responsible for cerebral malaria. Micro RNA ‐27a and micro RNA ‐146a are supposed to involve in cerebral malaria pathology. To assess the relationship of micro RNA SNP to cerebral malaria outcome, we performed TaqMan Genotyping Assays in 110 cerebral malaria and 207 uncomplicated malaria cases for three candidate micro RNA SNP s (rs895819 of micro RNA ‐27a, rs57095329 and rs2910164 of micro RNA ‐146a). Results Our study detected no significant difference in genotype and allele frequency of individual micro RNA SNP s as well as in haplotypes of micro RNA ‐146a between these two groups of malaria patients in Thailand. Hardy–Weinberg disequilibrium of rs57095329 in the cerebral malaria group showed a heterozygous excess which might be due to natural selection. Conclusion Our data supported that the candidate micro RNA SNP s have no major role to develop cerebral malaria.

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“…Malaria is one such disease that results in a spectrum of severity, from asymptomatic to fatal infection. Recently, Burel et al (2017) utilized a controlled human infection model to investigate the early molecular responses to malaria infection. They found that infected individuals could be stratified into two groups based on the changes in their circulating miRNA profile (low and high miR responders).…”

Section: Advantages Of Mirna Biomarkers Iv: Personalized Medicinementioning

confidence: 99%

“…They found that infected individuals could be stratified into two groups based on the changes in their circulating miRNA profile (low and high miR responders). Those patients in the high miR group were found to have increased CD4 + T-cell activation, a more robust antibody response, and reduced parasite burden (Burel et al, 2017). Importantly, the authors defined three miRNAs (miR-15a-3p, -30c-5p, and -30e-5p) that could distinguish these high and low-miR responders within days postinfection (Burel et al, 2017).…”

Section: Advantages Of Mirna Biomarkers Iv: Personalized Medicinementioning

confidence: 99%

MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing

et al. 2020

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In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18-22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.

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Dichotomous miR expression and immune responses following primary blood-stage malaria

Cited by 32 publications

References 44 publications

Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection

Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection

microRNA‐27a and microRNA‐146aSNPin cerebral malaria

MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing

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