Complement protein C3 binding to Bacillus anthracis spores enhances phagocytosis by human macrophages

Area of Science:

• Immunology
• Microbiology
• Pathogenesis

Background:

• Alveolar macrophages are key in inhalational anthrax pathogenesis.
• Mechanisms of Bacillus anthracis spore phagocytosis by macrophages are not fully understood.
• The role of lung-soluble factors like immunoglobulin and complement in spore uptake requires clarification.

Purpose of the Study:

• To investigate the involvement of immunoglobulin (IgG) and complement (C3) in Bacillus anthracis spore-macrophage interactions.
• To characterize the binding of human IgG and C3 to B. anthracis spores.
• To determine if these factors enhance spore phagocytosis by human macrophages.

Main Methods:

• Characterization of human IgG and C3 binding to B. anthracis spores using varying concentrations of nonimmune human serum.
• Investigation of B. anthracis spore uptake by human monocyte-derived macrophages in the presence of nonimmune human serum.

Main Results:

• C3b was found to bind to B. anthracis spores.
• IgG bound to the spore surface activated complement via the classical pathway.
• C3 acted as an opsonin, significantly enhancing B. anthracis spore phagocytosis by macrophages.
• Nonimmune human serum contained IgG that bound spores but was insufficient for phagocytosis alone.

Conclusions:

• Surface-bound IgG on B. anthracis spores triggers the classical complement pathway.
• Complement activation leads to C3b deposition, acting as an opsonin.
• Enhanced phagocytosis of B. anthracis spores by macrophages is mediated by C3b, a critical step in the host response to inhalational anthrax.