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Effects of Chronic Ascariasis and Trichuriasis on Cytokine Production and Gene Expression in Human Blood: A Cross-Sectional Study.

Reina Ortiz, M; Schreiber, F; Benitez, S; Broncano, N; Chico, ME; Vaca, M; Alexander, N; Lewis, DJ; Dougan, G; Cooper, PJ (2011) Effects of Chronic Ascariasis and Trichuriasis on Cytokine Production and Gene Expression in Human Blood: A Cross-Sectional Study. PLOS NEGLECTED TROPICAL DISEASES, 5 (6). e1157 - e1157 (10). ISSN 1935-2727 https://doi.org/10.1371/journal.pntd.0001157
SGUL Authors: Lewis, David John Murdoch Cooper, Philip John

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Abstract

Background Chronic soil-transmitted helminth (STH) infections are associated with effects on systemic immune responses that could be caused by alterations in immune homeostasis. To investigate this, we measured the impact in children of STH infections on cytokine responses and gene expression in unstimulated blood. Methodology/Principal Findings Sixty children were classified as having chronic, light, or no STH infections. Peripheral blood mononuclear cells were cultured in medium for 5 days to measure cytokine accumulation. RNA was isolated from peripheral blood and gene expression analysed using microarrays. Different infection groups were compared for the purpose of analysis: STH infection (combined chronic and light vs. uninfected groups) and chronic STH infection (chronic vs. combined light and uninfected groups). The chronic STH infection effect was associated with elevated production of GM-CSF (P = 0.007), IL-2 (P = 0.03), IL-5 (P = 0.01), and IL-10 (P = 0.01). Data reduction suggested that chronic infections were primarily associated with an immune phenotype characterized by elevated IL-5 and IL-10, typical of a modified Th2-like response. Chronic STH infections were associated with the up-regulation of genes associated with immune homeostasis (IDO, P = 0.03; CCL23, P = 0.008, HRK, P = 0.005), down-regulation of microRNA hsa-let-7d (P = 0.01) and differential regulation of several genes associated with granulocyte-mediated inflammation (IL-8, down-regulated, P = 0.0002; RNASE2, up-regulated, P = 0.009; RNASE3, up-regulated, p = 0.03). Conclusions/Significance Chronic STH infections were associated with a cytokine response indicative of a modified Th2 response. There was evidence that STH infections were associated with a pattern of gene expression suggestive of the induction of homeostatic mechanisms, the differential expression of several inflammatory genes and the down-regulation of microRNA has-let-7d. Effects on immune homeostasis and the development of a modified Th2 immune response during chronic STH infections could explain the systemic immunologic effects that have been associated with these infections such as impaired immune responses to vaccines and the suppression of inflammatory diseases.

Item Type: Article
Additional Information: Copyright: © 2011 Reina Ortiz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Ascariasis, Blood, Cells, Cultured, Child, Cross-Sectional Studies, Cytokines, Female, Gene Expression, Gene Expression Profiling, Humans, Leukocytes, Mononuclear, Male, Microarray Analysis, Trichuriasis, Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, Parasitology, Tropical Medicine, HUMAN LYMPHATIC FILARIASIS, IMMUNE HYPORESPONSIVENESS, SCHISTOSOMA-MANSONI, INFECTION, RESPONSES, CHILDREN, INTERLEUKIN-10, INDUCTION, PARASITES, CELLS
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: PLOS NEGLECTED TROPICAL DISEASES
ISSN: 1935-2727
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Dates:
DateEvent
1 June 2011Published
Web of Science ID: WOS:000292139600012
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URI: http://openaccess.sgul.ac.uk/id/eprint/102219
Publisher's version: https://doi.org/10.1371/journal.pntd.0001157

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