title: 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.affiliation: Bacterial Toxins and Therapeutics Section, Laboratory of Bacterial Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. shliu@niaid.nih.gov
authors.forename: Shihui
authors.initials: S
authors.lastname: Liu
authors.forename: Sharmina
authors.initials: S
authors.lastname: Miller-Randolph
authors.forename: Devorah
authors.initials: D
authors.lastname: Crown
authors.forename: Mahtab
authors.initials: M
authors.lastname: Moayeri
authors.forename: Inka
authors.initials: I
authors.lastname: Sastalla
authors.forename: Shu
authors.initials: S
authors.lastname: Okugawa
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
mesh_terms: D000818:Animals; D000881:Anthrax / Q000276:immunology / Q000382:microbiology; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000378:metabolism / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D009504:Neutrophils / Q000378:metabolism / Q000382:microbiology; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; C523013:Antxr2 protein, mouse; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin