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Effects of chronic ascariasis and trichuriasis on cytokine production and gene expression in human blood: a cross-sectional study.

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Reina Ortiz, Miguel, Schreiber, Fernanda, Benitez, Susana, Broncano, Nely, Chico, Martha E, Vaca, Maritza, Alexander, Neal, Lewis, David J, Dougan, Gordon and Cooper, Philip (2011) 'Effects of chronic ascariasis and trichuriasis on cytokine production and gene expression in human blood: a cross-sectional study.'. PLoS Neglected Tropical Diseases, Vol 5, Issue 6, e1157.

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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
Subjects: QX Parasitology > Helminths. Annelida > QX 200 Helminths
QY Clinical Pathology > Diagnostic Tests > QY 250 Immunodiagnostic tests
QY Clinical Pathology > Blood. Blood Chemistry > QY 400 General works
WA Public Health > Preventive Medicine > WA 110 Prevention and control of communicable diseases. Transmission of infectious diseases
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 870 Ascariasis
WS Pediatrics > Diseases of Children and Adolescents > General Diseases > WS 200 General works
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pntd.0001157
Depositing User: Mary Creegan
Date Deposited: 30 Sep 2011 15:06
Last Modified: 06 Feb 2018 13:04
URI: http://archive.lstmed.ac.uk/id/eprint/2345

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