Macrophage migrating inhibitory factor expression is associated with Trypanosoma brucei gambiense infection and is controlled by trans-acting expression quantitative trait loci in the Guinean population

Kaboré, J. W. et al. (2019) Macrophage migrating inhibitory factor expression is associated with Trypanosoma brucei gambiense infection and is controlled by trans-acting expression quantitative trait loci in the Guinean population. Infection, Genetics and Evolution, 71, pp. 108-115. (doi: 10.1016/j.meegid.2019.03.021) (PMID:30914286)

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Abstract

Infection by Trypanosoma brucei gambiense is characterized by a wide array of clinical outcomes, ranging from asymptomatic to acute disease and even spontaneous cure. In this study, we investigated the association between macrophage migrating inhibitory factor (MIF), an important pro-inflammatory cytokine that plays a central role in both innate and acquired immunity, and disease outcome during T. b. gambiense infection. A comparative expression analysis of patients, individuals with latent infection and controls found that MIF had significantly higher expression in patients (n = 141; 1.25 ± 0.07; p < .0001) and latent infections (n = 25; 1.23 ± 0.13; p = .0005) relative to controls (n = 46; 0.94 ± 0.11). Furthermore, expression decreased significantly after treatment (patients before treatment n = 33; 1.40 ± 0.18 versus patients after treatment n = 33; 0.99 ± 0.10, p = .0001). We conducted a genome wide eQTL analysis on 29 controls, 128 cases and 15 latently infected individuals for whom expression and genotype data were both available. Four loci, including one containing the chemokine CXCL13, were found to associate with MIF expression. Genes at these loci are candidate regulators of increased expression of MIF after infection. Our study is the first data demonstrating that MIF expression is elevated in T. b. gambiense-infected human hosts but does not appear to contribute to pathology.

Item Type:Articles
Additional Information:The authors would like to acknowledge also H3ABioNet, funded under grant number U41HG006941, for the data provided by their imputation service. This study was funded through the Wellcome Trust (study number 099310/Z/12/Z) awarded to the TrypanoGen Consortium, members of H3Africa (099310).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cooper, Dr Anneli and Matovu, Dr Enock and MacLeod, Professor Annette and Clucas, Dr Caroline and Capewell, Dr Paul
Authors: Kaboré, J. W., Camara, O., Ilboudo, H., Capewell, P., Clucas, C., Cooper, A., Kaboré, J., Camara, M., Jamonneau, V., Hertz-Fowler, C., Bélem, A. M. G., Matovu, E., Macleod, A., Sidibé, I., Noyes, H., and Bucheton, B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Infection, Genetics and Evolution
Publisher:Elsevier
ISSN:1567-1348
ISSN (Online):1567-7257
Published Online:23 March 2019
Copyright Holders:Copyright © 2019 Elsevier B.V.
First Published:First published in Infection, Genetics and Evolution 71:108-115
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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