title: Bordetella type III secretion and adenylate cyclase toxin synergize to drive dendritic cells into a semimature state.
abstract: Bordetella bronchiseptica establishes persistent infection of the murine respiratory tract. We hypothesize that long-term colonization is mediated in part by bacteria-driven modulation of dendritic cells (DCs) leading to altered adaptive immune responses. Bone marrow-derived DCs (BMDCs) from C57BL/6 mice infected with live B. bronchiseptica exhibited high surface expression of MHCII, CD86, and CD80. However, B. bronchiseptica-infected BMDCs did not exhibit significant increases in CD40 surface expression and IL-12 secretion compared with BMDCs treated with heat-killed B. bronchiseptica. The B. bronchiseptica type III secretion system (TTSS) mediated the increase in MHCII, CD86, and CD80 surface expression, while the inhibition of CD40 and IL-12 expression was mediated by adenylate cyclase toxin (ACT). IL-6 secretion was independent of the TTSS and ACT. These phenotypic changes may result from differential regulation of MAPK signaling in DCs. Wild-type B. bronchiseptica activated the ERK 1/2 signaling pathway in a TTSS-dependent manner. Additionally, ACT was found to inhibit p38 signaling. These data suggest that B. bronchiseptica drive DC into a semimature phenotype by altering MAPK signaling. These semimature DCs may induce tolerogenic immune responses that allow the persistent colonization of B. bronchiseptica in the host respiratory tract.
authors.affiliation: Department of Microbiology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Skinner
authors.forename: Annette
authors.initials: A
authors.lastname: Reissinger
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
authors.forename: Ming H
authors.initials: MH
authors.lastname: Yuk
mesh_terms: D037361:Adenylate Cyclase Toxin / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D001885:Bordetella Infections / Q000276:immunology* / Q000382:microbiology; D016950:Bordetella bronchiseptica / Q000276:immunology* / Q000502:physiology; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007108:Immune Tolerance; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis
chemical_list: D037361:Adenylate Cyclase Toxin; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D018664:Interleukin-12