title: Recognition of Coxiella burnetii by toll-like receptors and nucleotide-binding oligomerization domain-like receptors.
abstract: BACKGROUND
  Infection with Coxiella burnetii can lead to acute and chronic Q fever. Toll-like receptor 1 (TLR1), TLR2, TLR4, TLR6, nucleotide-binding oligomerization domain receptor 1 (NOD1), NOD2, and the mitogen-activated protein kinases are central in the innate immune response against microorganisms, but little is known about their role in the recognition of C. burnetii in humans.
  
  
  METHODS
  Human peripheral blood mononuclear cells (PBMCs) were stimulated with C. burnetii Nine Mile and the Dutch outbreak isolate C. burnetii 3262. TLRs were inhibited using specific antibodies or antagonists. Additionally, the influence of human polymorphisms in TLRs and Nod-like receptors (NLRs) on C. burnetii-induced cytokine production was assessed.
  
  
  RESULTS
  Inhibition of TLR2, p38, JNK, and ERK led to decreased cytokine responses in C. burnetii-stimulated human PBMCs. Humans with polymorphisms in TLR1 and NOD2 had reduced cytokine production, compared with humans with wild-type genotypes, after stimulation. Interestingly, polymorphisms in TLR6 led to decreased cytokine production after C. burnetii 3262 stimulation but not after C. burnetii Nine Mile stimulation.
  
  
  CONCLUSIONS
  The TLR1/TLR2 heterodimer and NOD2 are important recognition receptors for the induction of cytokine responses against C. burnetii in humans. Furthermore, an interesting finding was the divergent recognition of C. burnetii Nine Mile and C. burnetii 3262.
authors.affiliation: Department of Internal Medicine Department of Bacteriology and TSEs.
authors.forename: Anne
authors.initials: A
authors.lastname: Ammerdorffer
authors.affiliation: Department of Internal Medicine.
authors.forename: Teske
authors.initials: T
authors.lastname: Schoffelen
authors.affiliation: Department of Internal Medicine.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Gresnigt
authors.affiliation: Department of Internal Medicine.
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.affiliation: Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences.
authors.forename: Martijn H
authors.initials: MH
authors.lastname: den Brok
authors.affiliation: Department of Rheumatology.
authors.forename: Shahla
authors.initials: S
authors.lastname: Abdollahi-Roodsaz
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Thirumala-Devi
authors.initials: TD
authors.lastname: Kanneganti
authors.affiliation: Department of Gastroenterology, Radboud University Medical Center.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: de Jong
authors.affiliation: Department of Internal Medicine.
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
authors.affiliation: Department of Bacteriology and TSEs.
authors.forename: Hendrik-Jan
authors.initials: HJ
authors.lastname: Roest
authors.affiliation: Department of Infection Biology, Central Veterinary Institute, Lelystad, the Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Rebel
authors.affiliation: Department of Internal Medicine.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Department of Internal Medicine Department of Internal Medicine Department of Medical Microbiology and Infectious Diseases, CWZ, Nijmegen.
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D020935:MAP Kinase Signaling System; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology*; D053473:Nod2 Signaling Adaptor Protein / Q000502:physiology*; D051193:Toll-Like Receptors / Q000502:physiology*; D055815:Young Adult
chemical_list: D016207:Cytokines; C119067:NOD1 protein, human; C429018:NOD2 protein, human; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D051193:Toll-Like Receptors
keywords: Coxiella burnetii; NOD-like receptors; Q fever; Toll-like receptors; innate immunity; pattern recognition; single-nucleotide polymorphism