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Immunomodulation therapy offers new molecular strategies to treat UTI

Butler, Daniel LU ; Ambite, Ines LU orcid ; Wan, Murphy Lam Yim LU ; Tran, Thi Hien LU ; Wullt, Björn LU and Svanborg, Catharina LU (2022) In Nature Reviews Urology 19(7). p.419-437
Abstract

Innovative solutions are needed for the treatment of bacterial infections, and a range of antibacterial molecules have been explored as alternatives to antibiotics. A different approach is to investigate the immune system of the host for new ways of making the antibacterial defence more efficient. However, the immune system has a dual role as protector and cause of disease: in addition to being protective, increasing evidence shows that innate immune responses can become excessive and cause acute symptoms and tissue pathology during infection. This role of innate immunity in disease suggests that the immune system should be targeted therapeutically, to inhibit over-reactivity. The ultimate goal is to develop therapies that selectively... (More)

Innovative solutions are needed for the treatment of bacterial infections, and a range of antibacterial molecules have been explored as alternatives to antibiotics. A different approach is to investigate the immune system of the host for new ways of making the antibacterial defence more efficient. However, the immune system has a dual role as protector and cause of disease: in addition to being protective, increasing evidence shows that innate immune responses can become excessive and cause acute symptoms and tissue pathology during infection. This role of innate immunity in disease suggests that the immune system should be targeted therapeutically, to inhibit over-reactivity. The ultimate goal is to develop therapies that selectively attenuate destructive immune response cascades, while augmenting the protective antimicrobial defence but such treatment options have remained underexplored, owing to the molecular proximity of the protective and destructive effects of the immune response. The concept of innate immunomodulation therapy has been developed successfully in urinary tract infections, based on detailed studies of innate immune activation and disease pathogenesis. Effective, disease-specific, immunomodulatory strategies have been developed by targeting specific immune response regulators including key transcription factors. In acute pyelonephritis, targeting interferon regulatory factor 7 using small interfering RNA or treatment with antimicrobial peptide cathelicidin was protective and, in acute cystitis, targeting overactive effector molecules such as IL-1β, MMP7, COX2, cAMP and the pain-sensing receptor NK1R has been successful in vivo. Furthermore, other UTI treatment strategies, such as inhibiting bacterial adhesion and vaccination, have also shown promise.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Reviews Urology
volume
19
issue
7
pages
19 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:35732832
  • scopus:85132575361
ISSN
1759-4812
DOI
10.1038/s41585-022-00602-4
language
English
LU publication?
yes
id
76bdf84b-4130-428f-ae8a-6c26e73c435a
date added to LUP
2022-09-15 15:38:02
date last changed
2024-04-14 16:15:07
@article{76bdf84b-4130-428f-ae8a-6c26e73c435a,
  abstract     = {{<p>Innovative solutions are needed for the treatment of bacterial infections, and a range of antibacterial molecules have been explored as alternatives to antibiotics. A different approach is to investigate the immune system of the host for new ways of making the antibacterial defence more efficient. However, the immune system has a dual role as protector and cause of disease: in addition to being protective, increasing evidence shows that innate immune responses can become excessive and cause acute symptoms and tissue pathology during infection. This role of innate immunity in disease suggests that the immune system should be targeted therapeutically, to inhibit over-reactivity. The ultimate goal is to develop therapies that selectively attenuate destructive immune response cascades, while augmenting the protective antimicrobial defence but such treatment options have remained underexplored, owing to the molecular proximity of the protective and destructive effects of the immune response. The concept of innate immunomodulation therapy has been developed successfully in urinary tract infections, based on detailed studies of innate immune activation and disease pathogenesis. Effective, disease-specific, immunomodulatory strategies have been developed by targeting specific immune response regulators including key transcription factors. In acute pyelonephritis, targeting interferon regulatory factor 7 using small interfering RNA or treatment with antimicrobial peptide cathelicidin was protective and, in acute cystitis, targeting overactive effector molecules such as IL-1β, MMP7, COX2, cAMP and the pain-sensing receptor NK1R has been successful in vivo. Furthermore, other UTI treatment strategies, such as inhibiting bacterial adhesion and vaccination, have also shown promise.</p>}},
  author       = {{Butler, Daniel and Ambite, Ines and Wan, Murphy Lam Yim and Tran, Thi Hien and Wullt, Björn and Svanborg, Catharina}},
  issn         = {{1759-4812}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{419--437}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Reviews Urology}},
  title        = {{Immunomodulation therapy offers new molecular strategies to treat UTI}},
  url          = {{http://dx.doi.org/10.1038/s41585-022-00602-4}},
  doi          = {{10.1038/s41585-022-00602-4}},
  volume       = {{19}},
  year         = {{2022}},
}