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.

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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