Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.

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Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.

Ragnarsdottir, Bryndis (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Jönsson, Klas (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Urbano, Alexander (author)

Grönberg Hernandez, Jenny (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Urologi,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Urology,Lund University Research Groups

Lutay, Nataliya (author): Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine,Division of Microbiology, Immunology and Glycobiology - MIG

Tammi, Martti (author)

Gustafsson, Mattias (author): Lund University,Lunds universitet,Avdelningen för medicinsk mikrobiologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Medical Microbiology,Department of Laboratory Medicine,Faculty of Medicine

Lundstedt, Ann-Charlotte (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Leijonhufvud, Irene (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Reproduktionsmedicin, Malmö,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Reproductive medicine, Malmö,Lund University Research Groups

Karpman, Diana (author): Lund University,Lunds universitet,Pediatrik, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Pediatrisk nefrologi,Forskargrupper vid Lunds universitet,Paediatrics (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Pediatric Nephrology,Lund University Research Groups

Wullt, Björn (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Urologi,Forskargrupper vid Lunds universitet,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine,Urology,Lund University Research Groups

Truedsson, Lennart (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

Jodal, Ulf, 1938 (author): Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics

Andersson, Björn (author): Karolinska Institutet

Svanborg, Catharina (author): Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine

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2010-05-20
2010
English.
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:5

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Journal article (peer-reviewed)

Abstract Subject headings

BACKGROUND: Polymorphisms affecting Toll-like receptor (TLR) structure appear to be rare, as would be expected due to their essential coordinator role in innate immunity. Here, we assess variation in TLR4 expression, rather than structure, as a mechanism to diversify innate immune responses. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the TLR4 promoter (4,3 kb) in Swedish blood donors. Since TLR4 plays a vital role in susceptibility to urinary tract infection (UTI), promoter sequences were obtained from children with mild or severe disease. We performed a case-control study of pediatric patients with asymptomatic bacteriuria (ABU) or those prone to recurrent acute pyelonephritis (APN). Promoter activity of the single SNPs or multiple allelic changes corresponding to the genotype patterns (GPs) was tested. We then conducted a replication study in an independent cohort of adult patients with a history of childhood APN. Last, in vivo effects of the different GPs were examined after therapeutic intravesical inoculation of 19 patients with Escherichia coli 83972. We identified in total eight TLR4 promoter sequence variants in the Swedish control population, forming 19 haplotypes and 29 genotype patterns, some with effects on promoter activity. Compared to symptomatic patients and healthy controls, ABU patients had fewer genotype patterns, and their promoter sequence variants reduced TLR4 expression in response to infection. The ABU associated GPs also reduced innate immune responses in patients who were subjected to therapeutic urinary E. coli tract inoculation. CONCLUSIONS: The results suggest that genetic variation in the TLR4 promoter may be an essential, largely overlooked mechanism to influence TLR4 expression and UTI susceptibility.

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By the author/editor: Ragnarsdottir, B ...; Jönsson, Klas; Urbano, Alexande ...; Grönberg Hernand ...; Lutay, Nataliya; Tammi, Martti; show more...; Gustafsson, Matt ...; Lundstedt, Ann-C ...; Leijonhufvud, Ir ...; Karpman, Diana; Wullt, Björn; Truedsson, Lenna ...; Jodal, Ulf, 1938; Andersson, Björn; Svanborg, Cathar ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Neurology

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

Articles in the publication: PloS one

By the university: University of Gothenburg; Lund University; Karolinska Institutet

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Toll-like receptor 4 promoter polymorphisms: common TLR4 variants may protect against severe urinary tract infection.

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