scholarly journals Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder

2020 ◽  
Author(s):  
Livia Lacerda Mariano ◽  
Matthieu Rousseau ◽  
Hugo Varet ◽  
Rachel Legendre ◽  
Rebecca Gentek ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Infection Model ◽  
Bacterial Clearance ◽  
Resident Macrophage ◽  
Inflammatory Profile ◽  
Common Infection ◽  
Macrophage Subsets

SummaryResident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in the muscle and MacL in the lamina propria, with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to a more anti-inflammatory profile, whereas the MacL subset died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Depletion of these altered macrophages resulted in the induction of a type 1 biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their response to an exceedingly common infection in a largely overlooked organ, the bladder.

scholarly journals Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder

2020 ◽  
Vol 6 (48) ◽  
pp. eabc5739
Author(s):  
Livia Lacerda Mariano ◽  
Matthieu Rousseau ◽  
Hugo Varet ◽  
Rachel Legendre ◽  
Rebecca Gentek ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Infection Model ◽  
Resident Macrophage ◽  
Macrophage Depletion ◽  
Inflammatory Profile ◽  
Common Infection ◽  
Macrophage Subsets

Resident macrophages are abundant in the bladder, playing key roles in immunity to uropathogens. Yet, whether they are heterogeneous, where they come from, and how they respond to infection remain largely unknown. We identified two macrophage subsets in mouse bladders, MacM in muscle and MacL in the lamina propria, each with distinct protein expression and transcriptomes. Using a urinary tract infection model, we validated our transcriptomic analyses, finding that MacM macrophages phagocytosed more bacteria and polarized to an anti-inflammatory profile, whereas MacL macrophages died rapidly during infection. During resolution, monocyte-derived cells contributed to tissue-resident macrophage pools and both subsets acquired transcriptional profiles distinct from naïve macrophages. Macrophage depletion resulted in the induction of a type 1–biased immune response to a second urinary tract infection, improving bacterial clearance. Our study uncovers the biology of resident macrophages and their responses to an exceedingly common infection in a largely overlooked organ, the bladder.

scholarly journals Role of Ethanolamine Utilization Genes in Host Colonization during Urinary Tract Infection

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Anna Sintsova ◽  
Sara Smith ◽  
Sargurunathan Subashchandrabose ◽  
Harry L. Mobley
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Mouse Model ◽  
Virulence Determinants ◽  
Content Type ◽  
Immunocompromised Mouse ◽  
Common Infection ◽  
Increased Susceptibility

ABSTRACTUrinary tract infection (UTI) is the second most common infection in humans, making it a global health priority. Nearly half of all women will experience a symptomatic UTI, with uropathogenicEscherichia coli(UPEC) being the major causative agent of the infection. Although there has been extensive research on UPEC virulence determinants, the importance of host-specific metabolism remains understudied. We report here that UPEC upregulates the expression of ethanolamine utilization genes during uncomplicated UTIs in humans. We further show that UPEC ethanolamine metabolism is required for effective bladder colonization in the mouse model of ascending UTI and is dispensable for bladder colonization in an immunocompromised mouse model of UTI. We demonstrate that although ethanolamine metabolism mutants do not show increased susceptibility to antimicrobial responses of neutrophils, this metabolic pathway is important for surviving the innate immune system during UTI. This study reveals a novel aspect of UPEC metabolism in the host and provides evidence for an underappreciated link between bacterial metabolism and the host immune response.

scholarly journals In Vivo Dynamics of Type 1 Fimbria Regulation in UropathogenicEscherichia coli during Experimental Urinary Tract Infection

2001 ◽  
Vol 69 (5) ◽  
pp. 2838-2846 ◽  
Author(s):  
Nereus W. Gunther ◽  
Virginia Lockatell ◽  
David E. Johnson ◽  
Harry L. T. Mobley
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Invertible Element ◽  
Molecular Techniques ◽  
E Coli ◽  
Type 1 Fimbriae ◽  
Invertible Elements

ABSTRACT Escherichia coli is the primary cause of uncomplicated infections of the urinary tract including cystitis. More serious infections, characterized as acute pyelonephritis, can also develop. Type 1 fimbriae of E. coli contribute to virulence in the urinary tract; however, only recently has the expression of the type 1 fimbriae been investigated in vivo using molecular techniques. Transcription of type 1 fimbrial genes is controlled by a promoter that resides on a 314-bp invertible element capable of two orientations. One places the promoter in the ON orientation, allowing for transcription; the other places the promoter in the OFF orientation, preventing transcription. A PCR-based assay was developed to measure the orientation of the invertible element during an experimental urinary tract infection in mice. Using this assay, it was found that the percentage of the population ON in urine samples correlated with the respective CFU per gram of bladder (P = 0.0006) but not with CFU per gram of kidney (P > 0.069). Cystitis isolates present in the urine of mice during the course of infection had a higher percentage of their invertible elements in the ON orientation than did pyelonephritis isolates (85 and 34%, respectively, at 24 h; P < 0.0001). In general, cystitis isolates, unlike pyelonephritis isolates, were more likely to maintain their invertible elements in the ON orientation for the entire period of infection. E. coli cells expressing type 1 fimbriae, expelled in urine, were shown by scanning electron microscopy to be densely packed on the surface of uroepithelial cells. These results suggest that expression of type 1 fimbriae is more critical for cystitis strains than for pyelonephritis strains in the early stages of an infection during bladder colonization.

scholarly journals Efficacy of mecillinam against clinical multidrug-resistant Escherichia coli in a murine urinary tract infection model

2020 ◽  
Vol 55 (2) ◽  
pp. 105851
Author(s):  
Ilya Nikolaevich Zykov ◽  
Niels Frimodt-Møller ◽  
Lars Småbrekke ◽  
Arnfinn Sundsfjord ◽  
Ørjan Samuelsen
Keyword(s):  
Escherichia Coli ◽  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Multidrug Resistant ◽  
Infection Model

scholarly journals The Two-Component System GrvRS (EtaRS) RegulatesaceExpression in Enterococcus faecalis OG1RF

2014 ◽  
Vol 83 (1) ◽  
pp. 389-395 ◽  
Author(s):  
Jung Hyeob Roh ◽  
Kavindra V. Singh ◽  
Sabina Leanti La Rosa ◽  
Ana Luisa V. Cohen ◽  
Barbara E. Murray
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Regulatory System ◽  
Northern Hybridization ◽  
Infection Model ◽  
Content Type ◽  
Infection Models ◽  
Two Component ◽  
Main Regulator

Expression oface(adhesin tocollagen ofEnterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46°C. However, the mechanism oface/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator ofaceexpression under these stress conditions. Using Northern hybridization and β-galactosidase assays of anacepromoter-lacZfusion, we found transcription ofaceto be virtually absent in agrvRdeletion mutant under the conditions that increaseaceexpression in wild-type OG1RF and in the complemented strain. Moreover, agrvRmutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control ofaceexpression andE. faecalisvirulence.

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