Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus

PLoS Negl Trop Dis. 2016 Jul 27;10(7):e0004832. doi: 10.1371/journal.pntd.0004832. eCollection 2016 Jul.

Abstract

Background: Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels.

Methodology/principal findings: Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression.

Conclusions: This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Mucosal-Associated Invariant T Cells / physiology*
  • Scrub Typhus / metabolism
  • Scrub Typhus / pathology*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the National Research Foundation of Korea funded by the Korean Government (Grants 2013R1A2A2A01067956, 2015R1D1A4A01019017 and 2015R1D1A1A01059762) and the Chonnam National University Hospital Biomedical Research Institute (Grants CRI13905-22, CRI15003-1, CRI16036-21 and CRI16036-22). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.