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children, google, scholar, pubmed, article, levels, malaria, cas, falciparum, treatment, samples, ana, figure, blood, cytokine, nets, immune, response, net, neutrophil, crp, activity, presence, found, leukocyte, cells, analysis, plasmodium, slides, neutrophils, extracellular, differential, pretreatment, posttreatment, range, cell, tnf, authors, peripheral, patients, central, dna, tgfβ, elevated, significant, low, parasite, formation, high, immunol,

Topics {✒️}

springer nature author information authors gov/dpdx/html/imagelibrary/malaria_il stimulates il-12-ifn-γ-dependent activation ifn-γ-th1-dependent immune response protective molecules-c-reactive protein leukocyte differential count pro-inflammatory cytokines ifn-γ background pathogenesis world health mission day post-treatment follow authors’ original file leukocyte differential counts author correspondence human immunodeficiency virus-seropositive physician-based malaria team cell-mediated immune responses pre-sp-treatment samples revealed differential count falciparum-infected children pre-treatment transforming growth factor-beta1 information peripheral blood smears socio-economic factors responsible authors scientific editing leukocyte differential analysis slide-positive falciparum malaria post-treatment differential analysis thick/thin blood films uncomplicated falciparum malaria c-reactive protein t-cell clonal expansion pre-treatment leukocyte population florida state university neutrophil extracellular traps clinically uncomplicated slide-positive neutrophil toxic granulation leukocyte differential percentage current research team sequester free-circulating parasites ifn-γ box plot yield paradoxical results malaria clinical outreach/study plasmodium falciparum-infected children cytokines tested ifn-γ net-induced pamp activity privacy choices/manage cookies plasmodium falciparum malaria age-matched uninfected children stained control smears

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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         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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      name:Department of Biological Science, Florida State University, Tallahassee, USA
      name:Jos University Teaching Hospital and Medical School, Jos, Nigeria
      name:Jos University Teaching Hospital and Medical School, Jos, Nigeria
      name:Jos University Teaching Hospital and Medical School, Jos, Nigeria
      name:Jos University Teaching Hospital and Medical School, Jos, Nigeria
      name:Jos University Teaching Hospital and Medical School, Jos, Nigeria
      name:Nigerian Institute of Medical Research, Yaba, Nigeria
      name:Jackson Hospital, Marianna, USA
      name:World Health Mission, Pittsburgh, USA
      name:World Health Mission, Pittsburgh, USA
      name:Department of Biological Science, Florida State University, Tallahassee, USA
      name:Department of Biological Science, Florida State University, Tallahassee, USA

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