Modulation of activation-associated host cell gene expression by the apicomplexan parasite Theileria annulata

Durrani, Z., Weir, W. , Pillai, S., Kinnaird, J. and Shiels, B. (2012) Modulation of activation-associated host cell gene expression by the apicomplexan parasite Theileria annulata. Cellular Microbiology, 14(9), pp. 1434-1454. (doi:10.1111/j.1462-5822.2012.01809.x) (PMID:22533473) (PMCID:PMC3532605)

Durrani, Z., Weir, W. , Pillai, S., Kinnaird, J. and Shiels, B. (2012) Modulation of activation-associated host cell gene expression by the apicomplexan parasite Theileria annulata. Cellular Microbiology, 14(9), pp. 1434-1454. (doi:10.1111/j.1462-5822.2012.01809.x) (PMID:22533473) (PMCID:PMC3532605)

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Abstract

Infection of bovine leucocytes by Theileria annulata results in establishment of transformed, infected cells. Infection of the host cell is known to promote constitutive activation of pro-inflammatory transcription factors that have the potential to be beneficial or detrimental. In this study we have compared the effect of LPS activation on uninfected bovine leucocytes (BL20 cells) and their Theileria-infected counterpart (TBL20). Gene expression profiles representing activated uninfected BL20 relative to TBL20 cells were also compared. The results show that while prolonged stimulation with LPS induces cell death and activation of NF-κB in BL20 cells, the viability of Theileria-infected cells was unaffected. Analysis of gene expression networks provided evidence that the parasite establishes tight control over pathways associated with cellular activation by modulating reception of extrinsic stimuli and by significantly altering the expression outcome of genes targeted by infection-activated transcription factors. Pathway analysis of the data set identified novel candidate genes involved in manipulation of cellular functions associated with the infected transformed cell. The data indicate that the T. annulata parasite can irreversibly reconfigure host cell gene expression networks associated with development of inflammatory disease and cancer to generate an outcome thatis beneficial to survival and propagation of the infected leucocyte.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Weir, Dr William and Shiels, Professor Brian and Durrani, Mr Zeeshan and Kinnaird, Dr Jane
Authors: Durrani, Z., Weir, W., Pillai, S., Kinnaird, J., and Shiels, B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Cellular Microbiology
ISSN:1462-5814
ISSN (Online):1462-5822
Published Online:23 May 2012

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
465051Investigation of molecular mechanisms deployed by Theileria annulata as an activator and modulator of host cell transcription factors.Brian ShielsWellcome Trust (WELLCOME)083488/Z/07/ZIII - BACTERIOLOGY