Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis

Laperchia, C., Tesoriero, C., La Verde, V., Seke-Etet, P. F., Colavito, V., Grassi-Zucconi, G., Rodgers, J. , Montague, P., Kennedy, P. G.E. and Bentivoglio, M. (2017) Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis. PLoS Neglected Tropical Diseases, 11(8), e0005854. (doi:10.1371/journal.pntd.0005854) (PMID:28821016) (PMCID:PMC5576758)

[img]
Preview
Text
145452.pdf - Published Version
Available under License Creative Commons Attribution.

4MB

Abstract

Background: Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. Methodology/Principal findings: The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. Conclusions/Significance: The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Montague, Dr Paul and Kennedy, Professor Peter and Rodgers, Dr Jean
Authors: Laperchia, C., Tesoriero, C., La Verde, V., Seke-Etet, P. F., Colavito, V., Grassi-Zucconi, G., Rodgers, J., Montague, P., Kennedy, P. G.E., and Bentivoglio, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2017 Laperchia et al.
First Published:First published in PLoS Neglected Tropical Diseases 11(8):e0005854
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
554901Defining the role of kynurenine pathway metabolites in the inflammatory response to trypanosome invasion of the CNSPeter KennedyWellcome Trust (WELLCOTR)094691/Z/10/ZIII - PARASITOLOGY
523051Defining the role of the chemokine CXCL10 in determining traversal across the blood-brain barrier in experimental and human African trypanosomiasisPeter KennedyWellcome Trust (WELLCOTR)08992/Z/09/ZIII - PARASITOLOGY