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Molecular determinants of disease severity in urinary tract infection

Ambite, Ines LU orcid ; Butler, Daniel LU ; Wan, Murphy Lam Yim LU ; Rosenblad, Therese LU ; Tran, Thi Hien LU ; Chao, Sing Ming and Svanborg, Catharina LU (2021) In Nature Reviews Urology 18(8). p.468-486
Abstract

The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of... (More)

The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Reviews Urology
volume
18
issue
8
pages
468 - 486
publisher
Nature Publishing Group
external identifiers
  • scopus:85107905228
  • pmid:34131331
ISSN
1759-4812
DOI
10.1038/s41585-021-00477-x
language
English
LU publication?
yes
id
d683c0ef-da9b-4d1b-b204-8810124c2fbb
date added to LUP
2021-07-14 15:02:52
date last changed
2024-09-22 21:31:27
@article{d683c0ef-da9b-4d1b-b204-8810124c2fbb,
  abstract     = {{<p>The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.</p>}},
  author       = {{Ambite, Ines and Butler, Daniel and Wan, Murphy Lam Yim and Rosenblad, Therese and Tran, Thi Hien and Chao, Sing Ming and Svanborg, Catharina}},
  issn         = {{1759-4812}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{468--486}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Reviews Urology}},
  title        = {{Molecular determinants of disease severity in urinary tract infection}},
  url          = {{http://dx.doi.org/10.1038/s41585-021-00477-x}},
  doi          = {{10.1038/s41585-021-00477-x}},
  volume       = {{18}},
  year         = {{2021}},
}