Dataset Information

Circulating mucosal-associated invariant T cells in subjects with recurrent urinary tract infections are functionally impaired.

ABSTRACT:

Background

Urinary tract infection recurrence is common, particularly in women and immunocompromised patients, such as renal transplant recipients (RTRs). Mucosal-associated invariant T (MAIT) cells play a role in the antibacterial response by recognizing bacterial riboflavin metabolites produced by bacteria such as Escherichia coli. Here, we investigated whether MAIT cells are involved in the pathogenesis of recurrent urinary tract infections (RUTIs).

Methods

Using multichannel flow cytometry, we characterized the MAIT cell phenotype and function in blood from immunocompetent adults with (n = 13) and without RUTIs (n = 10) and in RTRs with (n = 9) and without RUTIs (n = 10).

Results

There were no differences in the numbers of MAIT cells between the study groups. MAIT cells in patients with RUTI expressed T-bet more often than those in controls. MAIT cells from immunocompetent RUTI participants required more antigen-presenting cells coincubated with E. coli to evoke a similar cytokine and degranulation response than those from controls. This effect was absent in the RTR with RUTI vs RTR control groups, where the overall percentage of MAIT cells that responded to stimulation was already reduced.

Conclusion

Circulating MAIT cells in immunocompetent individuals with RUTIs respond to bacterial stimuli with reduced efficacy, which suggests that they are involved in the pathogenesis of RUTIs.

SUBMITTER: Terpstra ML

PROVIDER: S-EPMC7016840 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Circulating mucosal-associated invariant T cells in subjects with recurrent urinary tract infections are functionally impaired.

Terpstra Matty L ML Remmerswaal Ester B M EBM van Aalderen Michiel C MC Wever Joyce J JJ Sinnige Marjan J MJ van der Bom-Baylon Nelly D ND Bemelman Frederike J FJ Geerlings Suzanne E SE

Immunity, inflammation and disease 20200207 1

<h4>Background</h4>Urinary tract infection recurrence is common, particularly in women and immunocompromised patients, such as renal transplant recipients (RTRs). Mucosal-associated invariant T (MAIT) cells play a role in the antibacterial response by recognizing bacterial riboflavin metabolites produced by bacteria such as Escherichia coli. Here, we investigated whether MAIT cells are involved in the pathogenesis of recurrent urinary tract infections (RUTIs).<h4>Methods</h4>Using multichannel f ...[more]

PMID: 32032475

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Project description:One in three women will experience a clinically significant urinary tract infection (UTI) by age twenty-four and almost half will have at least one in their lifetime. Recurrent UTIs (rUTIs) are defined as having greater than two infections in a 6-month period, or three infections over twelve months, with complete resolution for at least two weeks. These may be due to relapse from incomplete treatment (persistence) or re-infection (new source). It may be difficult to distinguish between the two, where the same organism is cultured. There are several risk factors for rUTIs including an impairment of the body's immune system and virulence factors. Reversible or treatable causes are sought and excluded in the patient's initial review. Patient's with rUTI are often complex and difficult to manage. The long-term management options in women are multimodal and should focus on prevention of relapse and recurrence. Behavioural factors include adequate hydration, care with sexual hygiene, reducing one's body mass index (BMI) and post-void residual (PVR) volume. There are several non-antimicrobial options for rUTIs which have become a multi-billion-dollar business. Unfortunately, there are numerous studies which fail to show any major benefit or having conflicting data. Vaccines are currently being explored as a prevention strategy, delivered through injection, intra-nasal sprays, or vaginal suppositories, which are made from combinations of heat killed uro-pathogenic strains. There are no widely available vaccines at present due to limited clinical success. It is well established that appropriate antibiotic therapy results in higher rates of symptom relief and bacterial eradication in women with uncomplicated cystitis. There are several options for antimicrobial use which have been shown to be highly effective in reducing the risk of rUTI in women. The pain and discomfort of the UTI must be balanced with the cost and risk of developing resistance when using antimicrobials. Continuous prophylaxis, pre- and post-coital voiding, and self-starting are the three commonly accepted options for prophylaxis. The choice between these will depend upon patient preference, cultures and previous pattern of infection. Intra-vesical instillation of hyaluronic acid and chondroitin sulphate have been used for glycosaminoglycan (GAG) layer replenishment for many indications, including interstitial cystitis, overactive bladder syndrome, radiation cystitis and prevention of rUTI. At present, intra-vesical therapies are reserved for only those with the most unresponsive rUTIs. The principles of treating rUTI are to break the cycle and to treat any reversible causes. With our ever-expanding research knowledge, there are now many useful products that may be used for the successful treatment of rUTI. A management plan including a combination of a non-antimicrobial and selective antimicrobial regime for a minimum of six months should be considered. It is a prudent clinician that clearly defines this management plan, with reassurance of a finite period of therapy.

Project description:ObjectiveTo compare recurrent urinary tract infection (rUTI) guidelines from major urological and non-urological organisations internationally and identify areas of consensus and discrepancy.MethodsPubMed, Google Scholar and the official webpages of major urological, gynaecological, infectious diseases and general practice organisations were searched for rUTI guidelines in March 2022. Nine guidelines were included for review: European Association of Urology, National Institute for Health and Care Excellence (NICE), Society of Obstetricians and Gynaecologists of Canada, American Academy of Family Physicians, Mexican College of Gynaecology and Obstetrics Specialists, Swiss Society of Gynaecology and Obstetrics, Spanish Society of Infectious Diseases and Clinical Microbiology, German Association of Scientific Medical Societies, and the combined American Urological Association/Canadian Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction.ResultsThe definition and evaluation of rUTIs, and antibiotic prophylaxis strategies, were mostly consistent across guidelines, and emphasised the importance of obtaining urine cultures and limiting cystoscopy and upper tract imaging in women without risk factors. Variable recommendations were noted for symptomatic treatment, self-initiated antibiotics, and antibiotic-sparing preventative strategies such as cranberry, vaginal oestrogen, immunoactive prophylaxis with OM-89, intravesical glycosaminoglycan instillation, and phytotherapeutics. Recent randomised evidence supports the use of methenamine hippurate. Either continuous or post-coital prophylactic antibiotics were supported by all guidelines. None of the guidelines were tailored to the management recurrent complicated UTI.ConclusionMultiple rUTI guidelines were identified and mostly limited their recommendations to otherwise healthy non-pregnant women with uncomplicated cystitis. Variation was noted, particularly in antibiotic-sparing preventative strategies. Some conflicting recommendations are due to more recent guidelines including updated evidence. Future guidelines should consider recommendations to assist management of complex patient groups, such as recurrent complicated UTI.

Dataset Information

Circulating mucosal-associated invariant T cells in subjects with recurrent urinary tract infections are functionally impaired.

Background

Methods

Results

Conclusion

Publications

Circulating mucosal-associated invariant T cells in subjects with recurrent urinary tract infections are functionally impaired.

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