Related Experiment Video
Updated: Jul 5, 2026

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
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.
Abstract:
The role of macrophages in the pathogenesis of anthrax is unresolved. Macrophages are believed to support the initiation of infection by Bacillus anthracis spores, yet are also sporicidal. Furthermore, it is believed that the anthrax toxins suppress normal macrophage function. However, the significance of toxin effects on macrophages has not been addressed in an in vivo infection model. We used mutant derivatives of murine macrophage RAW264.7 cells that are toxin receptor-negative (R3D) to test the role of toxin-targeting of macrophages during a challenge with spores of the Ames strain of B. anthracis in both in vivo and in vitro models. We found that the R3D cells were able to control challenge with Ames when mice were inoculated with the cells prior to spore challenge. These findings were confirmed in vitro by high dose spore infection of macrophages. Interestingly, whereas the R3D cells provided a significantly greater survival advantage against spores than did the wild type RAW264.7 cells or R3D-complemented cells, the protection afforded the mutant and wild type cells was equivalent against a bacillus challenge. The findings appear to be the first specific test of the role of toxin targeting of macrophages during infection with B. anthracis spores.
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.
More Related Videos
13:47Opsono-Adherence Assay to Evaluate Functional Antibodies in Vaccine Development Against Bacillus anthracis and Other Encapsulated Pathogens
Published on: May 19, 2020
10:01Quantification of Intracellular Growth Inside Macrophages is a Fast and Reliable Method for Assessing the Virulence of Leishmania Parasites
Published on: March 16, 2018
Related Concept Videos
Inhalation Anthrax
Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
Regulation of Bacterial Virulence
Receptor-mediated Endocytosis
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Tuberculosis
Cell-mediated Immune Responses