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Published on: October 1, 2012
Exposure to anthrax toxin alters human leucocyte expression of anthrax toxin receptor 1
R J Ingram1, A Harris, S Ascough
1Section of Infectious Diseases and Immunity, Department of Medicine Imperial College, Hammersmith Hospital, London.
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)-γ 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.
Insights
Anthrax toxin receptor ANTXR1 (TEM8) expression on human immune cells varies. Lower ANTXR1 expression correlates with higher interferon-gamma responses after infection, suggesting a protective mechanism against reinfection.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Anthrax toxin lethal effects depend on protective antigen (PA) binding to cell surface receptors (ANTXR).
- ANTXR binding influences host susceptibility and anthrax toxin immunomodulation.
- Limited data exists on ANTXR expression in human leukocytes.
Purpose of the Study:
- To characterize ANTXR1 (TEM8) expression on human leukocytes.
- To assess the impact of prior anthrax toxin exposure on ANTXR1 levels.
- To investigate the relationship between ANTXR1 expression and immune response.
Main Methods:
- Flow cytometry was used to analyze ANTXR1 expression on human leukocytes.
- Leukocytes were obtained from individuals with no known exposure, vaccinated individuals, and convalescent patients.
- Donors were classified as 'low' or 'high' expressers based on monocyte ANTXR1 positivity.
Main Results:
- ANTXR1 expression levels varied among individuals, allowing classification into 'low' and 'high' expressers.
- Prior anthrax toxin exposure modulated ANTXR1 expression.
- Active infection was associated with lower ANTXR1 expression.
- A significant correlation was found between low ANTXR1 expression and high anthrax toxin-specific interferon-gamma responses in previously infected individuals.
Conclusions:
- Anthrax toxin exposure, particularly infection, modulates ANTXR1 expression on human leukocytes.
- Reduced ANTXR1 expression post-infection may represent an evolved protective mechanism against reinfection.
- Further research into ANTXR1's role in anthrax immunity is warranted.
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