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Title:
Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age | Malaria Journal
Description:
Background In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Methods Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. Results The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. Conclusion The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.
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Keywords {🔍}
children, google, scholar, pubmed, article, levels, malaria, cas, falciparum, treatment, samples, ana, figure, blood, cytokine, nets, immune, response, net, neutrophil, plasmodium, crp, activity, presence, found, leukocyte, neutrophils, cells, analysis, slides, extracellular, differential, pretreatment, posttreatment, range, cell, peripheral, tnf, patients, dna, tgfβ, elevated, significant, low, parasite, formation, high, immunol, central, years,
Topics {✒️}
gov/dpdx/html/imagelibrary/malaria_il stimulates il-12-ifn-γ-dependent activation pro-inflammatory cytokines ifn-γ ifn-γ-th1-dependent immune response protective molecules-c-reactive protein world health mission human immunodeficiency virus-seropositive cell-mediated immune responses pre-sp-treatment samples revealed article download pdf physician-based malaria team florida state university transforming growth factor-beta1 socio-economic factors responsible peripheral blood smears falciparum-infected children pre-treatment leukocyte differential count thick/thin blood films c-reactive protein t-cell clonal expansion current research team leukocyte differential counts plasmodium falciparum infections sequester free-circulating parasites ifn-γ box plot post-treatment differential analysis pre-treatment leukocyte population slide-positive falciparum malaria neutrophil toxic granulation cytokines tested ifn-γ age-matched uninfected children net-induced pamp activity related subjects plasmodium falciparum-infected children stained control smears anti-nuclear antibody clinically uncomplicated slide-positive day post-treatment follow trained microscopists evaluated tris-edta buffer solution relating tgf-β levels anti-dsdna ana levels malaria clinical outreach/study high ifn-γ levels leukocyte differential analysis complement-fixing antibodies critical ratio threshold hemozoin-induced failure full access anti-erythrocyte activity
Questions {❓}
- Daniel-Ribeiro CT: Is there a role for autoimmunity in immune protection against malaria?
- Urban CF, Lourido S, Zychlinsky A: How do microbes evade neutrophil killing?
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headline:Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age
description:In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.
datePublished:2008-02-29T00:00:00Z
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Malaria
Falciparum Malaria
Neutrophil Extracellular Trap
Leukocyte Differential Count
Uncomplicated Falciparum Malaria
Parasitology
Tropical Medicine
Infectious Diseases
Entomology
Microbiology
Public Health
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headline:Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age
description:In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.
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Malaria
Falciparum Malaria
Neutrophil Extracellular Trap
Leukocyte Differential Count
Uncomplicated Falciparum Malaria
Parasitology
Tropical Medicine
Infectious Diseases
Entomology
Microbiology
Public Health
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