Early interactions between fully virulent Bacillus anthracis and macrophages that influence the balance between spore

Christopher K Cote1, Tracy L DiMezzo, David J Banks

  • 1Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA.

Insights

Macrophages are crucial in anthrax infection. Toxin-resistant macrophages (R3D) effectively controlled Bacillus anthracis spores in vivo and in vitro, unlike wild-type cells, highlighting toxin targeting

Area of Science:

  • Immunology
  • Microbiology
  • Pathogenesis

Background:

  • Macrophages play a dual role in Bacillus anthracis infection, potentially aiding initial infection and possessing sporicidal activity.
  • Anthrax toxins are thought to suppress macrophage function, but their in vivo impact on macrophages during infection remains unclear.

Purpose of the Study:

  • To investigate the specific role of anthrax toxin targeting of macrophages in the pathogenesis of B. anthracis spore infection.
  • To assess the efficacy of toxin receptor-negative (R3D) macrophages in controlling B. anthracis infection.

Main Methods:

  • Utilized toxin receptor-negative (R3D) mutant murine macrophage RAW264.7 cells and wild-type cells.
  • Tested macrophage efficacy against B. anthracis Ames strain spores and vegetative bacilli in both in vivo (mice) and in vitro models.

Main Results:

  • R3D macrophages demonstrated superior control of B. anthracis spore challenge compared to wild-type or complemented cells in vivo and in vitro.
  • Protection conferred by R3D and wild-type cells was comparable against vegetative B. anthracis bacilli challenge.

Conclusions:

  • Macrophage susceptibility to anthrax toxins significantly impacts the control of B. anthracis spore infections.
  • Targeting toxin receptors on macrophages represents a potential strategy for enhancing host defense against anthrax spores.

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