Pro-inflammatory Profile of MAIT cells in End Stage Renal Disease and Diabetes – Implications for TB Reactivation — ASN Events
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Pro-inflammatory Profile of MAIT cells in End Stage Renal Disease and Diabetes – Implications for TB Reactivation (#51)

Jennifer A Juno 1 , Jillian LM Waruk 2 , Carmen Lopez 1 , Joe Bueti 3 , T Blake Ball 1 2 , Sandra Kiazyk 1 2
  1. University of Manitoba, Winnipeg, MANITOBA, Canada
  2. Public Health Agency of Canada, Winnipeg, Manitoba, Canada
  3. Health Sciences Centre, Winnipeg, Manitoba, Canada

Background: End stage renal disease (ESRD) strongly increases the risk of Tuberculosis (TB) reactivation among those with latent Mycobacterium tuberculosis (Mtb) infection (LTBI). MAIT cell trafficking and cytokine production are implicated in the control of LTBI, but their function and phenotype in ESRD and associated co-morbidities (including diabetes) have not been defined. We assessed MAIT frequency, chemokine receptor expression and cytokine production in a Canadian ESRD cohort of latently infected and Mtb uninfected participants.

Methods: PBMC were collected from 10 participants in each of four study groups based on ESRD and LTBI status. MAIT cells were defined by flow cytometry based on expression of the Vα7.2 TCR, CD161 and CD26. Frequency and surface phenotype, including expression of CCR5, CCR6, CXCR3, and CXCR6, were quantified ex vivo. PBMC were stimulated with IL-12/IL-18, E. coli + IL-15 or PMA/Io to assess MAIT cell production of IFNγ, TNFα, GM-CSF and IL-17.

Results: ESRD participants exhibited decreased MAIT cell frequency compared to controls, as well as elevated surface expression of CCR6. While E. coli-induced MAIT cytokine production was comparable between groups, ESRD subjects exhibited elevated PMA-induced production of GM-CSF and reduced production of IFNγ, resulting in a shift in MAIT polyfunctionality and cytokine production. Ex vivo CCR6 expression correlated positively with GM-CSF and inversely with IFNγ production among all participants. Interestingly, diabetic participants exhibited reduced MAIT cell frequency and production of IFNγ following IL-12/IL-18 stimulation independently of ESRD status, suggesting unique impacts of each co-morbidity on MAIT cell function.

Implications: Current literature suggests that MAIT cells constitute an important component of the adaptive immune response to Mtb, and that a high GM-CSF/pro-inflammatory immune milieu may promote reactivation of LTBI. The altered frequency and bias of MAIT cells toward GM-CSF production, and away from IFNγ, in ESRD may contribute to poor control of Mtb latency.