title: Differential modulation of innate immune cell functions by the Burkholderia cepacia complex: Burkholderia cenocepacia but not Burkholderia multivorans disrupts maturation and induces necrosis in human dendritic cells.
abstract: Burkholderia cepacia complex (BCC) bacteria cause pulmonary infections that can evolve into fatal overwhelming septicemia in chronic granulomatous disease or cystic fibrosis patients. Burkholderia cenocepacia and Burkholderia multivorans are responsible for the majority of BCC infections in cystic fibrosis patients, but B. cenocepacia is generally associated with a poorer prognosis than B. multivorans. The present study investigated whether these pathogens could modulate the normal functions of primary human monocyte-derived dendritic cells (DCs), important phagocytic cells that act as critical orchestrators of the immune response. Effects of the bacteria on maturation of DCs were determined using flow cytometry. DCs co-incubated for 24 h with B. cenocepacia, but not B. multivorans, had reduced expression of costimulatory molecules when compared with standard BCC lipopolysaccharide-matured DCs. B. cenocepacia, but not B. multivorans, also induced necrosis in DCs after 24 h, as determined by annexin V and propidium iodide staining. DC necrosis only occurred after phagocytosis of live B. cenocepacia; DCs exposed to heat-killed bacteria, bacterial supernatant or those pre-treated with cytochalasin D then exposed to live bacteria remained viable. The ability of B. cenocepacia to interfere with normal DC maturation and induce necrosis may contribute to its pathogenicity in susceptible hosts.
authors.affiliation: Department of Microbiology and Immunology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: MacDonald
authors.forename: David P
authors.initials: DP
authors.lastname: Speert
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D042602:Burkholderia cepacia complex / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology*; D005434:Flow Cytometry; D006801:Humans; D009336:Necrosis; D011419:Propidium / Q000378:metabolism; D013194:Staining and Labeling
chemical_list: D017304:Annexin A5; D016207:Cytokines; D011419:Propidium