title: Toxin inhibition of antimicrobial factors induced by Bacillus anthracis peptidoglycan in human blood.
abstract: Here, we describe the capacity of Bacillus anthracis peptidoglycan (BaPGN) to trigger an antimicrobial response in human white blood cells (WBCs). Analysis of freshly isolated human blood cells found that monocytes and neutrophils, but not B and T cells, were highly responsive to BaPGN and produced a variety of cytokines and chemokines. This BaPGN-induced response was suppressed by anthrax lethal toxin (LT) and edema toxin (ET), with the most pronounced effect on human monocytes, and this corresponded with the higher levels of anthrax toxin receptor 1 (ANTXR1) in these cells than in neutrophils. The supernatant from BaPGN-treated cells altered the growth of B. anthracis Sterne, and this effect was blocked by LT, but not by ET. An FtsX mutant of B. anthracis known to be resistant to the antimicrobial effects of interferon-inducible Glu-Leu-Arg (ELR)-negative CXC chemokines was not affected by the BaPGN-induced antimicrobial effects. Collectively, these findings describe a system in which BaPGN triggers expression of antimicrobial factors in human WBCs and reveal a distinctive role, not shared with ET, in LT's capacity to suppress this response.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Soumitra
authors.initials: S
authors.lastname: Barua
authors.forename: Janaki K
authors.initials: JK
authors.lastname: Iyer
authors.forename: Jason L
authors.initials: JL
authors.lastname: Larabee
authors.forename: Brent
authors.initials: B
authors.lastname: Raisley
authors.forename: Molly A
authors.initials: MA
authors.lastname: Hughes
authors.forename: K Mark
authors.initials: KM
authors.lastname: Coggeshall
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Ballard
mesh_terms: D000328:Adult; D001408:Bacillus anthracis / Q000737:chemistry / Q000378:metabolism*; D001427:Bacterial Toxins / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D010457:Peptidoglycan / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D010457:Peptidoglycan