Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage-Colony Stimulating Factor Production During End-Stage Renal Disease

Juno, Jennifer A; Waruk, Jillian L.M.; Wragg, Kathleen; Mesa, Christine; Lopez, Carmen; Bueti, Joe; Kent, Stephen J.; Ball, T. Blake; Kiazyk, Sandra

doi:10.3389/fimmu.2018.01076

Cited by 15 publications

(25 citation statements)

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“…This is due to lowered sensitivity of the IGRA assay in detecting Mtb in ESRD groups which has been attributed to defective T cell function (272). γδ T cells in this co-infected population showed lowered expression of lung-homing receptors while MAIT cells were depleted in the periphery, with particular reductions in cells also associated with lung-trafficking (273,274). This indicates a potential role for unconventional T cells in controlling pulmonary TB infection.…”

Section: Antibodies and Immunity In Chronic Kidney Disease And Tubercmentioning

confidence: 94%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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Mycobacterium tuberculosis (Mtb) resides in a quarter of the world's population and is the causative agent for tuberculosis (TB), the most common infectious reason of death in humans today. Although cellular immunity has been firmly established in the control of Mtb, there is growing evidence that antibodies may also modulate the infection. More specifically, certain antibody features are associated with inflammation and are divergent in different states of human infection and disease. Importantly, TB impacts not just the healthy but also those with chronic conditions. While HIV represents the quintessential comorbid condition for TB, recent epidemiological evidence shows that additional chronic conditions such as diabetes and kidney disease are rising. In fact, the prevalence of diabetes as a comorbid TB condition is now higher than that of HIV. These chronic diseases are themselves independently associated with proinflammatory immune states that encompass antibody profiles. This review discusses isotypes, subclasses, post-translational modifications and Fc-mediated functions of antibodies in TB infection and in the comorbid chronic conditions of HIV, diabetes, and kidney diseases. We propose that inflammatory antibody profiles, which are a marker of active TB, may be an important biomarker for detection of TB disease progression within comorbid individuals. We highlight the need for future studies to determine which inflammatory antibody profiles are the consequences of comorbidities and which may potentially contribute to TB reactivation.

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Section: Antibodies and Immunity In Chronic Kidney Disease And Tubercmentioning

confidence: 94%

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

McLean

Kent

et al. 2019

Front. Immunol.

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“…In circulation, the number of MAIT cells was not decreased pre‐ or 12‐months post‐transplantation. This is in contrast with studies that describe fewer circulating MAIT cells in patients on dialysis and also after transplantation compared to healthy controls [24, 25]. This may be explained by methodological differences, since, in one study [24], MAIT cells were not identified based on TCR specificity but by the expression of CD3, CD161, and TCR Vα7.2 chain, and, in the other study [25], only CD8 + circulating MAIT cells were analyzed.…”

Section: Discussionmentioning

confidence: 63%

“…This is in contrast with studies that describe fewer circulating MAIT cells in patients on dialysis and also after transplantation compared to healthy controls [24, 25]. This may be explained by methodological differences, since, in one study [24], MAIT cells were not identified based on TCR specificity but by the expression of CD3, CD161, and TCR Vα7.2 chain, and, in the other study [25], only CD8 + circulating MAIT cells were analyzed. In both the latter and the present study, the activation state of circulating MAIT cells, assessed by CD69 expression [25] was elevated, both pre‐ and post‐transplantation.…”

Section: Discussionmentioning

confidence: 63%

“…Next, we evaluated the expression of chemokine receptors CXCR3 and CXCR6, which allow cells to migrate to distinct anatomic compartments such as the kidney [25, 37–41]. The percentage of MAIT cells expressing CXCR6 was lower in renal tissue compared with the circulating population (78.6% [58.3‐99.2%] vs. 89.1% [36.0‐98.5%], p = 0.045, and 46.7% [3.97‐93.4%] vs. 73.6% [14.2‐99.2%], p = 0.03, respectively), while the percentage of MAIT cells expressing CXCR3 was higher in the kidney (87.3% [54.5%‐99.0%] vs. 11.8% [1.82%‐77.7%], p < 0.001) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…UTIs are among the most common infection worldwide [20, 21], and immunocompromised patients, such as renal transplant recipients (RTRs) and patients with end‐stage renal disease (ESRD), are particularly vulnerable to UTIs [22, 23]. One of the factors underlying this enhanced vulnerability for UTIs in RTRs might be a decreased number of MAIT cells in circulation, as was recently shown both in patients with ESRD and RTRs years after transplantation [24–27]. However, little is known about the phenotype and function of (tissue‐resident) MAIT cells in healthy human kidneys or how they are affected by kidney transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Tissue‐resident mucosal‐associated invariant T (MAIT) cells in the human kidney represent a functionally distinct subset

et al. 2020

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Mucosal‐associated invariant T (MAIT) cells are innate‐like T‐cells that recognize bacterial riboflavin metabolites. They are present in human blood but are abundant at barrier sites, including the liver, lungs, and kidneys, where they possess a CD69+/CD103+/− tissue‐resident phenotype. In renal tissue, MAIT cells likely defend against the ascending uropathogens responsible for urinary tract infections (UTIs), which are common, especially among renal transplant recipients (RTRs). Nevertheless, the functional role for MAIT cells in renal tissue and the influence of renal transplantation on MAIT cells remains unclear. Using multiparameter flow cytometry and the MR1‐tetramer, we characterized MAIT cell phenotype and function in healthy renal tissue (n = 6), renal transplants explanted after allograft failure (n = 14) and in blood from healthy controls (n = 20) and RTRs before and 1‐year after transplantation (n = 21). MAIT cells in renal tissue constitute a distinct CD69+CD103+/− population that displays typical phenotypic features of tissue‐resident T‐cells and is skewed toward IL‐2, GM‐CSF, and IL‐17A production upon stimulation. The circulating MAIT cell population was not decreased in number in RTRs pre‐ or post‐transplantation. Tissue‐resident MAIT cells in the kidney represent a functionally distinct population. This shows how MAIT cells in the kidney may be involved in the protection against microorganisms.

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Serological and cellular inflammatory signatures in end‐stage kidney disease and latent tuberculosis

et al. 2021

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ObjectivesTuberculosis comorbidity with chronic diseases including diabetes, HIV and chronic kidney disease is of rising concern. In particular, latent tuberculosis infection (LTBI) comorbidity with end‐stage kidney disease (ESKD) is associated with up to 52.5‐fold increased risk of TB reactivation to active tuberculosis infection (ATBI). The immunological mechanisms driving this significant rise in TB reactivation are poorly understood. To contribute to this understanding, we performed a comprehensive assessment of soluble and cellular immune features amongst a unique cohort of patients comorbid with ESKD and LTBI.MethodsWe assessed the plasma and cellular immune profiles from patients with and without ESKD and/or LTBI (N = 40). We characterised antibody glycosylation, serum complement and cytokine levels. We also assessed classical and non‐classical monocytes and T cells with flow cytometry. Using a systems‐based approach, we identified key immunological features that discriminate between the different disease states.ResultsIndividuals with ESKD exhibited a highly inflammatory plasma profile and an activated cellular state compared with those without ESKD, including higher levels of inflammatory antibody Fc glycosylation structures and activated CX3CR1+ monocytes that correlate with increased inflammatory plasma cytokines. Similar elevated inflammatory signatures were also observed in ESKD+/LTBI+ compared with ESKD−/LTBI+, suggesting that ESKD induces an overwhelming inflammatory immune state. In contrast, no significant inflammatory differences were observed when comparing LTBI+ and LTBI− individuals.ConclusionOur study highlights the highly inflammatory state induced by ESKD. We hypothesise that this inflammatory state could contribute to the increased risk of TB reactivation in ESKD patients.

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Mucosal-Associated Invariant T Cells Are Depleted and Exhibit Altered Chemokine Receptor Expression and Elevated Granulocyte Macrophage-Colony Stimulating Factor Production During End-Stage Renal Disease

Cited by 15 publications

References 58 publications

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

An Inflammatory Story: Antibodies in Tuberculosis Comorbidities

Tissue‐resident mucosal‐associated invariant T (MAIT) cells in the human kidney represent a functionally distinct subset

Serological and cellular inflammatory signatures in end‐stage kidney disease and latent tuberculosis

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