Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice.

Abstract

Bacillus anthracis kills through a combination of bacterial infection and toxemia. Anthrax toxin working via the CMG2 receptor mediates lethality late in infection, but its roles early in infection remain unclear. We generated myeloid-lineage specific CMG2-deficient mice to examine the roles of macrophages, neutrophils, and other myeloid cells in anthrax pathogenesis. Macrophages and neutrophils isolated from these mice were resistant to anthrax toxin. However, the myeloid-specific CMG2-deficient mice remained fully sensitive to both anthrax lethal and edema toxins, demonstrating that targeting of myeloid cells is not responsible for anthrax toxin-induced lethality. Surprisingly, the myeloid-specific CMG2-deficient mice were completely resistant to B. anthracis infection. Neutrophil depletion experiments suggest that B. anthracis relies on anthrax toxin secretion to evade the scavenging functions of neutrophils to successfully establish infection. This work demonstrates that anthrax toxin uptake through CMG2 and the resulting impairment of myeloid cells are essential to anthrax infection.

• Authors: Shihui Liu, Sharmina Miller-Randolph, Devorah Crown, Mahtab Moayeri, Inka Sastalla, Shu Okugawa, Stephen H Leppla
• Journal: Cell host & microbe (Cell Host Microbe) Vol. 8 Issue 5 Pg. 455-62 (Nov 18 2010) ISSN: 1934-6069 [Electronic] United States
• PMID: 21075356 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Bacterial
• Antxr2 protein, mouse
• Bacterial Toxins
• Receptors, Peptide
• anthrax toxin

Topics

• Animals
• Anthrax (immunology, microbiology)
• Antigens, Bacterial (metabolism)
• Bacillus anthracis (metabolism, pathogenicity)
• Bacterial Toxins (metabolism)
• Host-Pathogen Interactions
• Macrophages (metabolism, microbiology)
• Mice
• Mice, Inbred C57BL
• Myeloid Cells (immunology, metabolism, microbiology)
• Neutrophils (metabolism, microbiology)
• Receptors, Peptide (genetics, metabolism)