title: Suppression of dendritic cell activation by anthrax lethal toxin and edema toxin depends on multiple factors including cell source, stimulus used, and function tested.
abstract: Bacillus anthracis produces lethal toxin (LT) and edema toxin (ET), and they suppress the function of LPS-stimulated dendritic cells (DCs). Because DCs respond differently to various microbial stimuli, we compared toxin effects in bone marrow DCs stimulated with either LPS or Legionella pneumophila (Lp). LT, not ET, was more toxic for cells from BALB/c than from C57BL/6 (B6) as measured by 7-AAD uptake; however, ET suppressed CD11c expression. LT suppressed IL-12, IL-6, and TNF-alpha in cells from BALB/c and B6 mice but increased IL-1beta in LPS-stimulated cultures. ET also suppressed IL-12 and TNF-alpha, but increased IL-6 and IL-1beta in Lp-stimulated cells from B6. Regarding maturation marker expression, LT increased MHCII and CD86 while suppressing CD40 and CD80; ET generally decreased marker expression across all groups. We conclude that the suppression of cytokine production by anthrax toxins is dependent on variables, including the source of the DCs, the type of stimulus and cytokine measured, and the individual toxin tested. However, LT and ET enhancement or suppression of maturation marker expression is more related to the marker studied than the stimuli or cell source. Anthrax toxins are not uniformly suppressive of DC function but instead can increase function under defined conditions.
authors.affiliation: Department of Molecular Medicine, University of South Florida College of Medicine, Tampa, Florida 33612, USA. pchou@health.usf.edu
authors.forename: Ping-Jen Joe
authors.initials: PJ
authors.lastname: Chou
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Newton
authors.forename: Izabella
authors.initials: I
authors.lastname: Perkins
authors.forename: Herman
authors.initials: H
authors.lastname: Friedman
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Klein
mesh_terms: D000262:Adenylyl Cyclases / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D004338:Drug Combinations; D007108:Immune Tolerance / Q000187:drug effects*; D007155:Immunologic Factors / Q000502:physiology*; D007158:Immunologic Techniques; D007877:Legionnaires' Disease / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D004338:Drug Combinations; D007155:Immunologic Factors; C030325:anthrax toxin; D000262:Adenylyl Cyclases