title: Exposure to Bacillus anthracis capsule results in suppression of human monocyte-derived dendritic cells.
abstract: The antiphagocytic capsule of Bacillus anthracis is a major virulence factor. We hypothesized that it may also mediate virulence through inhibition of the host's immune responses. During an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. We sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (iDCs). Human monocytes were differentiated into iDCs by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) over 7 days in the presence of capsule derived from wild-type encapsulated B. anthracis Ames (WT) or a control preparation from an isogenic B. anthracis Ames strain that produces only 2% of the capsule of the WT (capA mutant). WT capsule consistently induced release of IL-8 and IL-6 while the capA mutant control preparation elicited either no response or only a minimal release of IL-8. iDCs that were differentiated in the presence of WT capsule had increased side scatter (SSC), a measure of cellular complexity, when assessed by flow cytometry. iDCs differentiated in the presence of WT capsule also matured less well in response to subsequent B. anthracis peptidoglycan (Ba PGN) exposure, with reduced upregulation of the chemokine receptor CCR7, reduced CCR7-dependent chemotaxis, and reduced release of certain cytokines. Exposure of naive differentiated control iDCs to WT capsule did not alter cell surface marker expression but did elicit IL-8. These results indicate that free capsule may contribute to the pathogenesis of anthrax by suppressing the responses of immune cells and interfering with the maturation of iDCs.
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA tanya.obreiter@us.army.mil arthur.friedlander@us.army.mil.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Jelacic
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Chabot
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Bozue
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Tobery
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: West
authors.affiliation: Department of Microbiology, Boston University, School of Medicine, Boston, Massachusetts, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Moody
authors.affiliation: Laboratory of Molecular Immunoregulation, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
authors.forename: De
authors.initials: D
authors.lastname: Yang
authors.affiliation: Laboratory of Molecular Immunoregulation, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
authors.forename: Joost J
authors.initials: JJ
authors.lastname: Oppenheim
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA tanya.obreiter@us.army.mil arthur.friedlander@us.army.mil.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Friedlander
mesh_terms: D001408:Bacillus anthracis / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8