title: Pasteurella multocida toxin (PMT) activates RhoGTPases, induces actin polymerization and inhibits migration of human dendritic cells, but does not influence macropinocytosis.
abstract: Dendritic cells (DCs) are considered as one of the principal initiators of immune responses. In their immature state, they migrate into peripheral tissue in order to uptake antigen and to patrol for danger signals. Upon maturation, they acquire the ability to migrate to the lymph nodes and present the captured antigens to T cells in order to direct the development of specific immune responses. There is evidence that microbial compounds interfere with proper functions of DCs in order to block innate and specific immunity. Here we characterized the influence of Pasteurella multocida toxin (PMT) on monocyte-derived DCs. Using pull-down assays with recombinant rhotekin or p21-activated kinase, we demonstrated the activation of RhoGTPases by PMT in DCs. Moreover, PMT induced changes in DC morphology and actin polymerization, impaired chemotaxin-induced actin re-organization and inhibited their migration response. However, macropinocytosis was not influenced by PMT. In summary, these data indicate that PMT inhibits proper function of the motility machinery in DCs, which might limit the development of adaptive immune surveillance during infection with Pasteurella multocida.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Blöcker
authors.forename: Luciana
authors.initials: L
authors.lastname: Berod
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Fluhr
authors.forename: Joachim
authors.initials: J
authors.lastname: Orth
authors.forename: Marco
authors.initials: M
authors.lastname: Idzko
authors.forename: Klaus
authors.initials: K
authors.lastname: Aktories
authors.forename: Johannes
authors.initials: J
authors.lastname: Norgauer
mesh_terms: D000199:Actins / Q000737:chemistry*; D001426:Bacterial Proteins / Q000502:physiology*; D001427:Bacterial Toxins; D002465:Cell Movement; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D016979:Pasteurella multocida / Q000502:physiology; D010873:Pinocytosis; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C062258:Pasteurella multocida toxin; D020741:rho GTP-Binding Proteins