PMID:22442442

Citation	Gu, C, Jenkins, SA, Xue, Q and Xu, Y (2012) Activation of the classical complement pathway by Bacillus anthracis is the primary mechanism for spore phagocytosis and involves the spore surface protein BclA. J. Immunol. 188:4421-31
Abstract	Interactions between spores of Bacillus anthracis and macrophages are critical for the development of anthrax infections, as spores are thought to use macrophages as vehicles to disseminate in the host. In this study, we report a novel mechanism for phagocytosis of B. anthracis spores. Murine macrophage-like cell line RAW264.7, bone marrow-derived macrophages, and primary peritoneal macrophages from mice were used. The results indicated that activation of the classical complement pathway (CCP) was a primary mechanism for spore phagocytosis. Phagocytosis was significantly reduced in the absence of C1q or C3. C3 fragments were found deposited on the spore surface, and the deposition was dependent on C1q and Ca(2+). C1q recruitment to the spore surface was mediated by the spore surface protein BclA, as recombinant BclA bound directly and specifically to C1q and inhibited C1q binding to spores in a dose-dependent manner. C1q binding to spores lacking BclA (ΔbclA) was also significantly reduced compared with wild-type spores. In addition, deposition of both C3 and C4 as well as phagocytosis of spores were significantly reduced when BclA was absent, but were not reduced in the absence of IgG, suggesting that BclA, but not IgG, is important in these processes. Taken together, these results support a model in which spores actively engage CCP primarily through BclA interaction with C1q, leading to CCP activation and opsonophagocytosis of spores in an IgG-independent manner. These findings are likely to have significant implications on B. anthracis pathogenesis and microbial manipulation of complement.
Links	PubMed PMC3331890 Online version:10.4049/jimmunol.1102092
Keywords	Animals; Anthrax/genetics; Anthrax/immunology; Antibodies, Bacterial/genetics; Antibodies, Bacterial/immunology; Bacillus anthracis/physiology; Cell Line; Complement C1q/genetics; Complement C1q/immunology; Complement C3/genetics; Complement C3/immunology; Complement Pathway, Classical/genetics; Complement Pathway, Classical/immunology; Immunoglobulin G/genetics; Immunoglobulin G/immunology; Macrophages/immunology; Membrane Glycoproteins/genetics; Membrane Glycoproteins/immunology; Mice; Mice, Knockout; Phagocytosis/immunology; Spores, Bacterial/genetics; Spores, Bacterial/immunology
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
BACAN:Q81JD7	involved_in	GO:0050764: regulation of phagocytosis	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
BACAN:Q81JD7		GO:0006958: complement activation, classical pathway	ECO:0000314:		P		figure 5 demonstrated that the presence of BclA protein significantly enhance the C3 deposition on the spore surface; C3 is a critical components in classical complement pathway	complete CACAO 4094
BACAN:Q81JD7		GO:0050764: regulation of phagocytosis	ECO:0000314:		P		Figure 7 "suggested BclA is required for complement-mediated phagocytosis of spores"	complete CACAO 4095

References

See Help:References for how to manage references in GONUTS.