title: Host susceptibility and clinical outcomes in toll-like receptor 5-deficient patients with typhoid fever in Vietnam.
abstract: Toll-like receptor 5 (TLR5) mediates innate immune responses to bacterial pathogens by binding to flagellin. A polymorphism in the TLR5 gene introduces a premature stop codon (TLR5(392STOP)) that is associated with susceptibility to legionnaires disease. Here we investigated whether TLR5(392STOP) was associated with typhoid fever. The frequency of TLR5(392STOP) was not significantly different in 565 patients with typhoid fever and 281 ethnically matched control subjects. Furthermore, TLR5 deficiency had no measurable effect on a number of clinical parameters associated with typhoid fever, including fever clearance time, pathogen burden, disease severity, or age at acquisition of disease. TLR5 may not play an important role in TLR-stimulated innate immune responses to human infection with Salmonella enterica serovar Typhi. Initiation of these responses may rely on other TLRs that recognize different bacterial ligands.
authors.affiliation: Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. sdunstan@hcm.vnn.vn
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dunstan
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Hawn
authors.forename: Nguyen Thi
authors.initials: NT
authors.lastname: Hue
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Parry
authors.forename: Vo An
authors.initials: VA
authors.lastname: Ho
authors.forename: Ha
authors.initials: H
authors.lastname: Vinh
authors.forename: To Song
authors.initials: TS
authors.lastname: Diep
authors.forename: Deborah
authors.initials: D
authors.lastname: House
authors.forename: John
authors.initials: J
authors.lastname: Wain
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.forename: Tran Tinh
authors.initials: TT
authors.lastname: Hien
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Farrar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005408:Flagellin / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007223:Infant; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics*; D019779:Salmonella enterica / Q000472:pathogenicity*; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014435:Typhoid Fever / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D014744:Vietnam
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D005408:Flagellin