The immune response to infection in the bladder

Mariano, Lívia Lacerda; Ingersoll, Molly A.

doi:10.1038/s41585-020-0350-8

Cited by 90 publications

(75 citation statements)

References 269 publications

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“…The molecular determinants of disease severity in acute cystitis have been unclear; however, mechanisms of innate immune hyper-activation have now been identified using a combination of cellular infection technology, animal models and clinical studies 30 , 33 , 35 . The results show that acute cystitis is an IL-1β-driven, hyperinflammatory disorder of the infected urinary bladder driven by atypical IL-1β processing through matrix metalloproteinase 7 (MMP7) 33 (Fig.…”

Section: Acute Cystitismentioning

confidence: 99%

“…Early studies demonstrated that bladder epithelial cells produce cytokines in response to infection; a novel concept at the time 93 , 165 , 192 , 193 . Since then, numerous cytokines and chemokines have been detected in the urinary tract that mediate different aspects of the disease response 30 , 194 – 198 . The pro-inflammatory cytokine TNF, is rapidly and transiently expressed during the first days of infection 165 , 195 and supports neutrophil recruitment and bacterial clearance in a mouse model of UTI 199 .…”

Section: Acute Cystitismentioning

confidence: 99%

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Molecular determinants of disease severity in urinary tract infection

et al. 2021

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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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Section: Acute Cystitismentioning

confidence: 99%

Section: Acute Cystitismentioning

confidence: 99%

Molecular determinants of disease severity in urinary tract infection

et al. 2021

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“…The growth of E. coli in urine leads to different gene expression compared to the use of LB medium [ 34 ], and it cannot be ruled out that the phage receptors may be affected as well. Furthermore, urine may contain natural human antibacterial molecules and immune cells [ 35 ] which could support or modify the in vivo activity of phages. Similarly, antimicrobial therapy combined with phage therapy may provide additional benefits [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli

Slobodníková

Markusková

Kajsik

et al. 2021

Viruses

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Urinary tract infections (UTIs) are among the events that most frequently need medical intervention. Uropathogenic Escherichia coli are frequently their causative agents and the infections are sometimes complicated by the presence of polyresistant nosocomial strains. Phage therapy is a tool that has good prospects for the treatment of these infections. In the present study, we isolated and characterized two bacteriophages with broad host specificity against a panel of local uropathogenic E. coli strains and combined them into a phage cocktail. According to genome sequencing, these phages were closely related and belonged to the Tequatrovirus genus. The newly isolated phages showed very good activity on a panel of local clinical E. coli strains from urinary tract infections. In the form of a two-phage cocktail, they were active on E. coli strains belonging to phylogroups B2 and D, with relatively lower activity in B1 and no response in phylogroup A. Our study is a preliminary step toward the establishment of a national phage bank containing local, well-characterized phages with therapeutic potential for patients in Slovakia.

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“…Other host factors, mainly immune-related, also play a prominent role in the chronicity of rUTI, as the recurrence of infection is frequently associated with a disturbed innate immune response and/or insufficient adaptive immunity (recently reviewed in ( Lacerda Mariano and Ingersoll, 2020 ). The reasons behind these events are still unclear and largely unexplored due to the lack of knowledge about how the immune response is triggered and develops in human UTIs, which can differ significantly from the murine context.…”

Section: The Mechanisms Of Recurrent Uti: a Multi-faceted Problemmentioning

confidence: 99%

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Murray

Flores

Williams

et al. 2021

Front. Cell. Infect. Microbiol.

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Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.

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The immune response to infection in the bladder

Cited by 90 publications

References 269 publications

Molecular determinants of disease severity in urinary tract infection

Molecular determinants of disease severity in urinary tract infection

Characterization of Anti-Bacterial Effect of the Two New Phages against Uropathogenic Escherichia coli

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

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