title: Virulent Coxiella burnetii does not activate human dendritic cells: role of lipopolysaccharide as a shielding molecule.
abstract: Coxiella burnetii is an obligate intracellular bacterium and the etiological agent of the zoonotic disease Q fever. Acute human Q fever is characterized by flu-like symptoms that, in some cases, can result in a persistent infection that may reactivate months or years after initial exposure. Mechanisms by which this obligate parasite evades clearance by the host immune response during persistent infection are unknown. Here, we characterized the interaction of C. burnetii with dendritic cells (DC), critical components of both innate and adaptive immunity. Human DC were infected with two isogenic C. burnetii strains that differ in LPS length. Infection by the Nine Mile phase I (NMI) strain, which is fully virulent and produces full-length LPS, did not result in DC maturation. In contrast, infection by the avirulent Nine Mile phase II strain, producing a severely truncated LPS, resulted in toll-like receptor 4-independent DC maturation and approximately 10-fold more IL-12 and TNF production. NMI did not actively inhibit DC maturation as NMI-infected DC subsequently matured if treated with Escherichia coli LPS or Nine Mile phase II. Furthermore, removal of LPS from NMI dramatically increased its ability to stimulate DC. We propose a model whereby LPS of virulent C. burnetii masks toll-like receptor ligands from innate immune recognition by DC, thereby allowing replication without significant maturation or inflammatory cytokine production. This immune evasion strategy may allow C. burnetii to persist in an immunocompetent host.
authors.affiliation: Coxiella Pathogenesis Section, Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Shannon
authors.forename: Dale
authors.initials: D
authors.lastname: Howe
authors.forename: Robert A
authors.initials: RA
authors.lastname: Heinzen
mesh_terms: D016997:Coxiella burnetii / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D017931:DNA Primers; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D018664:Interleukin-12 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000096:biosynthesis* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000378:metabolism; D011778:Q Fever / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D017931:DNA Primers; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D021122:Protein Subunits; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12