Mast Cell Interleukin-10 Drives Localized Tolerance in Chronic Bladder Infection

Chan, Cheryl; John, Ashley L. St.; Abraham, Soman N.

doi:10.1016/j.immuni.2012.10.019

Cited by 141 publications

(174 citation statements)

References 60 publications

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“…Notably, in a different disease setting, and using both Kit W-sh/W-sh mice and Mcpt5-Cre + ; Il10 fl/fl mice, Chan et al (38) provided evidence that MC production of IL-10 can suppress humoral and cell-mediated responses and enhance bacterial persistence in a mouse model of bladder infection with E. coli. The findings of Chan et al (38) thus indicate that MC production of IL-10 also can contribute to suppression of inflammation in sites other than the skin.…”

Section: Discussionmentioning

confidence: 99%

Imaging protective mast cells in living mice during severe contact hypersensitivity

Reber¹,

Sibilano²,

Starkl³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Imaging protective mast cells in living mice during severe contact hypersensitivity

Reber¹,

Sibilano²,

Starkl³

et al. 2017

JCI Insight

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“…Thus, immunological differences, such as lower antibody concentrations, between the bladder and kidneys may explain the disparity in vaccine efficacy between tissues. Indeed, despite being prone to recurrent infection, the immunological networks of the bladder are distinct from those of the kidney and remain poorly defined (43). Therefore, it may be possible to extend the protection of the FyuA vaccine to the bladder by modifying the immunization route, formula, adjuvant, or timeline to improve the adaptive immune response in the bladder.…”

Section: Figmentioning

confidence: 99%

Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection

et al. 2015

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The emergence and spread of extended-spectrum beta-lactamases and carbapenemases among common bacterial pathogens are threatening our ability to treat routine hospital-and community-acquired infections. With the pipeline for new antibiotics virtually empty, there is an urgent need to develop novel therapeutics. Bacteria require iron to establish infection, and specialized pathogen-associated iron acquisition systems like yersiniabactin, common among pathogenic species in the family Enterobacteriaceae, including multidrug-resistant Klebsiella pneumoniae and pathogenic Escherichia coli, represent potentially novel therapeutic targets. Although the yersiniabactin system was recently identified as a vaccine target for uropathogenic E. coli (UPEC)-mediated urinary tract infection (UTI), its contribution to UPEC pathogenesis is unknown. Using an E. coli mutant (strain 536⌬fyuA) unable to acquire yersiniabactin during infection, we established the yersiniabactin receptor as a UPEC virulence factor during cystitis and pyelonephritis, a fitness factor during bacteremia, and a surface-accessible target of the experimental FyuA vaccine. In addition, we determined through transcriptome sequencing (RNA-seq) analyses of RNA from E. coli causing cystitis in women that iron acquisition systems, including the yersiniabactin system, are highly expressed by bacteria during natural uncomplicated UTI. Given that yersiniabactin contributes to the virulence of several pathogenic species in the family Enterobacteriaceae, including UPEC, and is frequently associated with multidrug-resistant strains, it represents a promising novel target to combat antibiotic-resistant infections.W idespread and increasing antibiotic resistance among bacterial pathogens that cause some of our most common health care-associated and community-acquired infections is jeopardizing our ability to prevent and treat routine infectious diseases (1). Two pathogens of particular concern are uropathogenic Escherichia coli (UPEC), which causes the majority (80%) of uncomplicated urinary tract infections (UTI) (2), and Klebsiella pneumoniae, a frequent cause of hospital-acquired pneumonia and UTI (3). Without adequate treatment, both UPEC and K. pneumoniae can breach epithelial and endothelial barriers to gain access to the bloodstream, causing life-threatening bacteremia (4). E. coli rates of resistance to fluoroquinolones and third-generation cephalosporins now exceed 50% in 5 of 6 global regions, and similar resistance rates were reported for K. pneumoniae worldwide (5). Unfortunately, the treatment of severe infections caused by these species must rely on carbapenems, the last resort to treat severe community-and hospital-acquired infections (6). Not only are these antibacterial compounds more expensive and less available in resource-constrained settings, but their extended use contributes to the spread of carbapenem-resistant Enterobacteriaceae (CRE), a serious global public health concern (7).Increasing rates of antimicrobial resistance and limited new therapeut...

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“…The functions of MCs were long thought to be limited to their role in allergy. Data generated using the 'mast cell knock-in' approach have changed this view, by providing evidence that MCs can, among other functions, play critical roles in host defense against certain pathogens 4,39 or venoms 28,31 , or can even suppress certain immune responses 29,34,40 .…”

Section: Discussionmentioning

confidence: 99%

Analyzing the Functions of Mast Cells <em>In Vivo</em> Using '<em>Mast Cell Knock-in</em>' Mice

Gaudenzio

Sibilano

Starkl

et al. 2015

JoVE

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Mast cells (MCs) are hematopoietic cells which reside in various tissues, and are especially abundant at sites exposed to the external environment, such as skin, airways and gastrointestinal tract. Best known for their detrimental role in IgE-dependent allergic reactions, MCs have also emerged as important players in host defense against venom and invading bacteria and parasites. MC phenotype and function can be influenced by microenvironmental factors that may differ according to anatomic location and/or based on the type or stage of development of immune responses. For this reason, we and others have favored in vivo approaches over in vitro methods to gain insight into MC functions. Here, we describe methods for the generation of mouse bone marrow-derived cultured MCs (BMCMCs), their adoptive transfer into genetically MC-deficient mice, and the analysis of the numbers and distribution of adoptively transferred MCs at different anatomical sites. This method, named the 'mast cell knock-in' approach, has been extensively used over the past 30 years to assess the functions of MCs and MC-derived products in vivo. We discuss the advantages and limitations of this method, in light of alternative approaches that have been developed in recent years. Video LinkThe video component of this article can be found at

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Mast Cell Interleukin-10 Drives Localized Tolerance in Chronic Bladder Infection

Cited by 141 publications

References 60 publications

Imaging protective mast cells in living mice during severe contact hypersensitivity

Imaging protective mast cells in living mice during severe contact hypersensitivity

Blocking Yersiniabactin Import Attenuates Extraintestinal Pathogenic Escherichia coli in Cystitis and Pyelonephritis and Represents a Novel Target To Prevent Urinary Tract Infection

Analyzing the Functions of Mast Cells <em>In Vivo</em> Using '<em>Mast Cell Knock-in</em>' Mice

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