Bacillus anthracis virulence – primary cellular target: Each of the three major virulence factors of Bacillus anthracis (poly-D-glutamate capsule, edema toxin, and lethal toxin) most directly alters the activity of which host cell type?

Introduction / Context:
Bacillus anthracis, the causative agent of anthrax, uses a triad of virulence factors—an antiphagocytic capsule and two binary exotoxins (edema toxin and lethal toxin)—to subvert innate immunity. Understanding which host cell type is primarily targeted clarifies how anthrax progresses from local exposure to systemic disease.

Given Data / Assumptions:

• Virulence factors: capsule, edema toxin (protective antigen + edema factor), and lethal toxin (protective antigen + lethal factor).
• Key early responders in tissue infection are phagocytes such as macrophages and dendritic cells.
• Toxins enter cells via protective antigen–mediated translocation.

Concept / Approach:
Macrophages are central to anthrax pathogenesis. Edema factor is a calmodulin-dependent adenylate cyclase that elevates intracellular cAMP, impairing phagocyte function and promoting edema. Lethal factor is a zinc-dependent metalloprotease that cleaves MAP kinase kinases, triggering macrophage dysfunction and lysis with downstream cytokine dysregulation. The poly-D-glutamate capsule blocks phagocytosis, further neutralizing macrophage defenses. Together, these mechanisms specifically undermine macrophage activity and permit bacterial survival and dissemination.

Step-by-Step Solution:
Identify the principal innate immune cell encountering B. anthracis at portals of entry: macrophages.Map toxin actions: edema factor raises cAMP → impairs phagocyte killing; lethal factor cleaves MAPKK → macrophage death/inflammation.Note capsule function: antiphagocytic barrier primarily thwarting macrophages.Conclude the dominant affected host cell is the macrophage.

Verification / Alternative check:
Experimental models demonstrate that toxin-mediated macrophage dysfunction precedes bacteremia and is essential for high-grade virulence, confirming macrophages as the key cellular target.

Why Other Options Are Wrong:

• B cells: not the primary toxin targets in early infection.
• Ciliated epithelial cells: anthrax toxins do not specifically target mucociliary clearance.
• M cells: important in gut sampling but not the main anthrax toxin target.
• Neutrophils: affected indirectly; macrophages are more directly compromised by toxin mechanisms.

Common Pitfalls:
Assuming capsules primarily affect epithelial barriers instead of phagocytosis; overlooking the protective antigen–mediated entry step that focuses toxin effects within phagocytes.

Final Answer:
Macrophages.