In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence, and disease severity remain poorly understood. This investigation relates levels of the pro-inflammatory cytokines IFN-g, IL-2, TNF-a, CRP, and IL-6, and select anti-inflammatory cytokines TGF-b and IL-10 to the formation of neutrophil extracellular nets (NETs), IgG antinuclear antibodies (ANA), and IgG antineutrophil cytoplasmic antibodies (ANCA) in blood collected before and seven days after initiation of Sulfadoxine-Pyrimethamine treatment from 21 Nigerian children under six years old presenting with uncomplicated malaria. The children exhibited a Th2 dominated cytokine profile and left-shifted leukocyte differential. Elevated TNF-a levels correlated with significant NET formation evident in the peripheral blood smears. ANA levels (inclusive of all subsets of ANA) 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. IgG ANA subset levels to dsDNA were significant in 81% of both the pre- and post treatment samples, whereas ANCA levels were positive in only 14% of both the pre-and post-treatment samples. Our results suggest that an inverse relationship between TGF-b and CRP levels may contribute to homeostasis and that TNF-a-associated NET formation and ANA may induce pathology in falciparum-infected children or activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and ANA to dsDNA as a causative factor in the hyporesponsiveness of CpG olignucleotide-based malaria vaccines is discussed. / A Dissertation submitted to the Department of Biological Science in partial
fulfillment of the requirements for the degree of Doctor of Philosophy. / Degree Awarded: Spring Semester, 2007. / Date of Defense: April 5, 2007. / Anti-Neutrophil Cytoplasmic Antibodies, Innate Immune Protection, ANA, ANCA, Neutrophil Extracellular Traps, Falciparum Malaria, Vaccine Hyporesponsiveness, Nets, Anti-Nuclear Antibodies, Autoimmunity, Cytokines / Includes bibliographical references. / Thomas Keller, III, Professor Directing Dissertation; Qing-Xiang Sang, Outside Committee Member; Robert H. Reeves, Committee Member; Kenneth H. Roux, Committee Member; Wu-Min Deng, Committee Member.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_169204 |
| Contributors | Baker, Virginia Stephens (authoraut), Keller, Thomas (professor directing dissertation), Sang, Qing-Xiang (outside committee member), Reeves, Robert H. (committee member), Roux, Kenneth H. (committee member), Deng, Wu-Min (committee member), Department of Biological Science (degree granting department), Florida State University (degree granting institution) |
| Publisher | Florida State University, Florida State University |
| Source Sets | Florida State University |
| Language | English, English |
| Detected Language | English |
| Type | Text, text |
| Format | 1 online resource, computer, application/pdf |
| Rights | This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). The copyright in theses and dissertations completed at Florida State University is held by the students who author them. |
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