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Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1

Lookup NU author(s): Professor John Robinson

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Abstract

Anthrax is a toxin-mediated disease, the lethal effects of which are initiated by the binding of protective antigen (PA) with one of three reported cell surface toxin receptors (ANTXR). Receptor binding has been shown to influence host susceptibility to the toxins. Despite this crucial role for ANTXR in the outcome of disease, and the reported immunomodulatory consequence of the anthrax toxins during infection, little is known about ANTXR expression on human leucocytes. We characterized the expression levels of ANTXR1 (TEM8) on human leucocytes using flow cytometry. In order to assess the effect of prior toxin exposure on ANTXR1 expression levels, leucocytes from individuals with no known exposure, those exposed to toxin through vaccination and convalescent individuals were analysed. Donors could be defined as either low' or high' expressers based on the percentage of ANTXR1-positive monocytes detected. Previous exposure to toxins appears to modulate ANTXR1 expression, exposure through active infection being associated with lower receptor expression. A significant correlation between low receptor expression and high anthrax toxin-specific interferon (IFN)- responses was observed in previously infected individuals. We propose that there is an attenuation of ANTXR1 expression post-infection which may be a protective mechanism that has evolved to prevent reinfection.


Publication metadata

Author(s): Ingram RJ, Harris A, Ascough S, Metan G, Doganay M, Ballie L, Williamson ED, Dyson H, Robinson JH, Sriskandan S, Altmann DM

Publication type: Article

Publication status: Published

Journal: Clinical and Experimental Immunology

Year: 2013

Volume: 173

Issue: 1

Pages: 84-91

Print publication date: 01/07/2013

Online publication date: 06/06/2013

Acceptance date: 05/02/2013

ISSN (print): 0009-9104

ISSN (electronic): 1365-2249

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1111/cei.12090

DOI: 10.1111/cei.12090


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Funding

Funder referenceFunder name
National Institute for Health Research Biomedical Research
HHSN266200400084CNational Institutes of Health, National Institute of Allergy and Infectious Diseases

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