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https://doi.org/10.1371/journal.pone.0028289
Title: | Genetic control of the variable innate immune response to asymptomatic bacteriuria | Authors: | Hernández J.G. Sundén F. Connolly J. Svanborg C. Wullt B. |
Keywords: | chemokine cytokine eotaxin gamma interferon inducible protein 10 interferon regulatory factor 3 interleukin 12p40 interleukin 1alpha interleukin 2 receptor alpha interleukin 6 interleukin 8 monocyte chemotactic protein 1 RANTES toll like receptor 4 adult aged article asymptomatic bacteriuria controlled study disease predisposition Escherichia coli female genetic regulation genetic variability genotype human immune response innate immunity inoculation male neutrophil count protein determination protein polymorphism quantitative analysis signal transduction urinary tract infection Adult Aged Bacteriuria Chemokines Escherichia coli Female Humans Immunity, Innate Interleukin-6 Interleukin-8 Leukocytes Male Middle Aged Polymorphism, Genetic Promoter Regions, Genetic Proteome |
Issue Date: | 2011 | Publisher: | Public Library of Science | Citation: | Hernández J.G., Sundén F., Connolly J., Svanborg C., Wullt B. (2011). Genetic control of the variable innate immune response to asymptomatic bacteriuria. PLoS ONE 6 (11) : e28289. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0028289 | Abstract: | The severity of urinary tract infection (UTI) reflects the quality and magnitude of the host response. While strong local and systemic innate immune activation occurs in patients with acute pyelonephritis, the response to asymptomatic bacteriuria (ABU) is low. The immune response repertoire in ABU has not been characterized, due to the inherent problem to distinguish bacterial differences from host-determined variation. In this study, we investigated the host response to ABU and genetic variants affecting innate immune signaling and UTI susceptibility. Patients were subjected to therapeutic urinary tract inoculation with E. coli 83972 to ensure that they were exposed to the same E. coli strain. The innate immune response repertoire was characterized in urine samples, collected from each patient before and after inoculation with bacteria or PBS, if during the placebo arm of the study. Long-term E. coli 83972 ABU was established in 23 participants, who were followed for up to twelve months and the innate immune response was quantified in 233 urine samples. Neutrophil numbers increased in all but two patients and in an extended urine cytokine/chemokine analysis (31 proteins), the chemoattractants IL-8 and GRO-α, RANTES, Eotaxin-1 and MCP-1, the T cell chemoattractant and antibacterial peptide IP-10, inflammatory regulators IL-1-α and sIL-1RA and the T lymphocyte/dendritic cell product sIL-2Rα were detected and variably increased, compared to sterile samples. IL-6, which is associated with symptomatic UTI, remained low and numerous specific immune mediators were not detected. The patients were also genotyped for UTI-associated IRF3 and TLR4 promoter polymorphisms. Patients with ABU associated TLR4 polymorphisms had low neutrophil numbers, IL-6, IP-10, MCP-1 and sIL-2Rα concentrations. Patients with the ABU-associated IRF3 genotype had lower neutrophils, IL-6 and MCP-1 responses than the remaining group. The results suggest that the host-specific, low immune response to ABU mainly includes innate immune mediators and that host genetics directly influence the magnitude of this response. © 2011 Hernández et al. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/165584 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0028289 |
Appears in Collections: | Elements Staff Publications |
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