Journal article
Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract
Journal of bacteriology, Vol.198(6), pp.964-972
01/11/2016
DOI: 10.1128/JB.00664-15
PMCID: PMC4772593
PMID: 26755631
Abstract
Urinary tract infection (UTI) is one of the most common ailments requiring both short-term and prophylactic antibiotic therapies. Progression of infection from the bladder to the kidney is associated with more severe clinical symptoms (e.g., fever and vomiting) as well as with dangerous disease sequelae (e.g., renal scaring and sepsis). Host-pathogen interactions that promote bacterial ascent to the kidney are not completely understood. Prior studies indicate that the magnitude of proinflammatory cytokine elicitation in vitro by clinical isolates of uropathogenic Escherichia coli (UPEC) inversely correlates with the severity of clinical disease. Therefore, we hypothesize that the magnitude of initial proinflammatory responses during infection defines the course and severity of disease. Clinical UPEC isolates obtained from patients with a nonfebrile UTI elicited high systemic proinflammatory responses early during experimental UTI in a murine model and were attenuated in bladder and kidney persistence. Conversely, UPEC isolates obtained from patients with febrile UTI elicited low systemic proinflammatory responses early during experimental UTI and exhibited prolonged persistence in the bladder and kidney. Soluble factors in the supernatant from saturated cultures as well as the lipopolysaccharide (LPS) serotype correlated with the magnitude of proinflammatory responses in vitro. Our data suggest that the structure of the O-antigen sugar moiety of the LPS may determine the strength of cytokine induction by epithelial cells. Moreover, the course and severity of disease appear to be the consequence of the magnitude of initial cytokines produced by the bladder epithelium during infection.
The specific host-pathogen interactions that determine the extent and course of disease are not completely understood. Our studies demonstrate that modest changes in the magnitude of cytokine production observed using in vitro models of infection translate into significant ramifications for bacterial persistence and disease severity. While many studies have demonstrated that modifications of the LPS lipid A moiety modulate the extent of Toll-like receptor 4 (TLR4) activation, our studies implicate the O-antigen sugar moiety as another potential rheostat for the modulation of proinflammatory cytokine production.
Details
- Title: Subtitle
- Association of O-Antigen Serotype with the Magnitude of Initial Systemic Cytokine Responses and Persistence in the Urinary Tract
- Creators
- Dennis J Horvath Jr - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USAAshay S Patel - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA Nationwide Children's Hospital, Columbus, Ohio, USAAhmad Mohamed - Nationwide Children's Hospital, Columbus, Ohio, USADouglas W Storm - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA Nationwide Children's Hospital, Columbus, Ohio, USAChandra Singh - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA Nationwide Children's Hospital, Columbus, Ohio, USABirong Li - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USAJingwen Zhang - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USAStephen A Koff - Nationwide Children's Hospital, Columbus, Ohio, USA The Ohio State University School of Medicine, Columbus, Ohio, USAVenkata R Jayanthi - Nationwide Children's Hospital, Columbus, Ohio, USA The Ohio State University School of Medicine, Columbus, Ohio, USAKevin M Mason - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA The Ohio State University School of Medicine, Columbus, Ohio, USASheryl S Justice - The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA The Ohio State University School of Medicine, Columbus, Ohio, USA Sheryl.justice@nationwidechildrens.org
- Resource Type
- Journal article
- Publication Details
- Journal of bacteriology, Vol.198(6), pp.964-972
- Publisher
- United States
- DOI
- 10.1128/JB.00664-15
- PMID
- 26755631
- PMCID
- PMC4772593
- ISSN
- 0021-9193
- eISSN
- 1098-5530
- Language
- English
- Date published
- 01/11/2016
- Academic Unit
- Stead Family Department of Pediatrics; Urology
- Record Identifier
- 9984051594102771
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