title: A role for TLR1, TLR2 and NOD2 in cytokine induction by Bacteroides fragilis.
abstract: Bacteroides fragilis, an intestinal flora commensal microorganism, is frequently isolated from abscesses and soft tissue infections. This study aimed to identify pattern recognition receptors (PRRs) involved in B. fragilis recognition and to characterize the induced cytokine profile. Human PBMCs were stimulated with heat-killed B. fragilis and cytokine levels were determined by ELISA. Roles of individual PRRs were assessed using specific blockers of receptor signaling pathways and PBMCs carrying single nucleotide polymorphisms of PRR genes. Cell lines expressing human TLR2 or TLR4 were employed to assess TLR-specificity of B. fragilis. TLR1, TLR2 and NOD2 were the main PRRs responsible for recognition of B. fragilis, while TLR4, TLR6, NOD1 and Dectin-1 were not involved. B. fragilis induced strong IL-6 and IL-8, moderate IL-1β and TNF-α, and poor IL-10, IL-17, IL-23 and IFN-γ production. This study identifies the receptor pathways of the innate immune response to B. fragilis, and thus provides new insights in the host defense against B. fragilis.
authors.affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Mark H T
authors.initials: MH
authors.lastname: Stappers
authors.forename: Nico A F
authors.initials: NA
authors.lastname: Janssen
authors.forename: Marije
authors.initials: M
authors.lastname: Oosting
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: Pierre
authors.initials: P
authors.lastname: Arvis
authors.forename: Johan W
authors.initials: JW
authors.lastname: Mouton
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Inge C
authors.initials: IC
authors.lastname: Gyssens
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001442:Bacteroides Infections / Q000276:immunology / Q000378:metabolism; D001441:Bacteroides fragilis / Q000276:immunology*; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D051194:Toll-Like Receptor 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D053473:Nod2 Signaling Adaptor Protein; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D000099181:Dectin-1; C429018:NOD2 protein, human; C495342:TLR2 protein, human