title: Genetic variation in TLR10 is not associated with chronic Q fever, despite the inhibitory effect of TLR10 on Coxiella burnetii-induced cytokines in vitro.
abstract: Coxiella burnetii, the causative agent of Q fever, is recognized by TLR2. TLR10 can act as an inhibitory receptor on TLR2-derived immune responses. Therefore, we investigated the role of TLR10 on C. burnetii-induced cytokine production and assessed whether genetic polymorphisms in TLR10 influences the development of chronic Q fever. HEK293 cells, transfected with TLR2, TLR10 or TLR2/TLR10, and human peripheral blood mononuclear cells (PBMCs) in the presence of anti-TLR10, were stimulated with C. burnetii. In both assays, the absence of TLR10 resulted in increased cytokine responses after C. burnetii stimulation. In addition, the effect of single nucleotide polymorphisms (SNPs) in TLR10 was examined in healthy volunteers whose PBMCs were stimulated with C. burnetii Nine Mile or the Dutch outbreak isolate C. burnetii 3262. Individuals bearing SNPs in TLR10 displayed increased cytokine production upon C. burnetii 3262 stimulation. Furthermore, 139 chronic Q fever patients and 220 controls were genotyped for TLR10 N241H, I775V and I369L. None of these polymorphisms were associated with increased susceptibility to chronic Q fever. In conclusion, TLR10 has an inhibitory effect on in vitro cytokine production by C. burnetii, but the presence of TLR10 polymorphisms does not lead to an increased risk of developing chronic Q fever.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; Department of Bacteriology and TSEs, Central Veterinary Institute, 8219 PH Lelystad, The Netherlands.
authors.forename: Anne
authors.initials: A
authors.lastname: Ammerdorffer
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; Hasselt University, 3500 Hasselt, Belgium; Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Ziekenhuis, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Mark H T
authors.initials: MH
authors.lastname: Stappers
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Teske
authors.initials: T
authors.lastname: Schoffelen
authors.affiliation: Department of Surgery, Jeroen Bosch Hospital, 5223 GW 's-Hertogenbosch, The Netherlands.
authors.forename: Julia C J P
authors.initials: JC
authors.lastname: Hagenaars
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Chantal P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.affiliation: Department of Medical Microbiology, Laboratory for Pathology and Medical Microbiology (PAMM), 5504 DL Veldhoven, The Netherlands.
authors.forename: Marjolijn C
authors.initials: MC
authors.lastname: Wegdam-Blans
authors.affiliation: Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 5223 GW 's-Hertogenbosch, The Netherlands.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Wever
authors.affiliation: Department of Bacteriology and TSEs, Central Veterinary Institute, 8219 PH Lelystad, The Netherlands.
authors.forename: Hendrik-Jan
authors.initials: HJ
authors.lastname: Roest
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands; Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Ziekenhuis, 6532 SZ Nijmegen, The Netherlands; Department of Internal Medicine, Canisius Wilhelmina Ziekenhuis, 6532 SZ Nijmegen, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands. Electronic address: Leo.Joosten@radboudumc.nl.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000145:classification / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D057809:HEK293 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011778:Q Fever / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology; D012307:Risk Factors; D013045:Species Specificity; D051201:Toll-Like Receptor 10 / Q000235:genetics*; D055815:Young Adult
chemical_list: D016207:Cytokines; C475955:TLR10 protein, human; D051201:Toll-Like Receptor 10
keywords: Coxiella burnetii; Innate immunity; Q fever; Single nucleotide polymorphism; Toll-like receptor 10