title: Effects of Clostridium difficile toxin B on human monocytes and macrophages: possible relationship with cytoskeletal rearrangement.
abstract: Toxin B from Clostridium difficile is cytopathic in vitro for various types of cells, including polymorphonuclear cells, lymphocytes, and monocytes. Since intestine lamina propria is rich in macrophages, we studied the effect of toxin B on human monocytes and on human macrophages generated in vitro by long-term culture of purified circulating blood monocytes. Upon addition of toxin B, human monocytes exhibited few modifications whereas macrophages adopted a stellate morphology, with rounding up of the perikaryon. Toxin B made microfilaments of actin disappear and induced an important reorganization of vimentin and a redistribution of tubulin. Membrane area increased by approximately 16%. Toxin B did not affect the viability of human mononuclear phagocytes and did not exert any significant lytic effect. It profoundly altered the phagocytic function of macrophages. When activated by gamma interferon in the presence of toxin B, monocytes were more cytotoxic for U-937 target cells than control monocytes activated in absence of toxin. Finally, the combined treatment of monocytes with gamma interferon and toxin B increased significantly the secretion of tumor necrosis factor alpha, whereas toxin B alone was unable to induce tumor necrosis factor production. These results suggest that morphological and functional alterations induced in human mononuclear phagocytes by toxin B from C. difficile are due to the disorganization of the cytoskeleton and the resulting impairment of the membrane traffic equilibrium.
authors.affiliation: Département d'Immunologie, Immunopharmacologie et Pathologie, Université Louis Pasteur, Illkirch, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Siffert
authors.forename: O
authors.initials: O
authors.lastname: Baldacini
authors.forename: J G
authors.initials: JG
authors.lastname: Kuhry
authors.forename: D
authors.initials: D
authors.lastname: Wachsmann
authors.forename: S
authors.initials: S
authors.lastname: Benabdelmoumene
authors.forename: A
authors.initials: A
authors.lastname: Faradji
authors.forename: H
authors.initials: H
authors.lastname: Monteil
authors.forename: P
authors.initials: P
authors.lastname: Poindron
mesh_terms: D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure*; D004761:Enterocolitis, Pseudomembranous / Q000209:etiology / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010587:Phagocytosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D014409:Tumor Necrosis Factor-alpha; C031815:toxB protein, Clostridium difficile; D007371:Interferon-gamma