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

Seung-Ji Kang,Hye-Mi Jin,Hee-Chang Jang,Hyun-Ju Jung,Eun Jeong Won,Young-Nan Cho,Hae Jin Kee,Jae Kyun Ju,Jung-Chul Kim,Yong-Wook Park,Sook-In Jung,Yong-Soo Kwon,Uh Jin Kim,Seung-Jung Kee,Benjamin L Makepeace

doi:10.1371/journal.pntd.0004832

Abstract

BackgroundMucosal-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 FindingsThirty-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.ConclusionsThis 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.

Highlights

Scrub typhus is a mite-borne bacterial infection in humans caused by Orientia tsutsugamushi, an obligate intracellular bacterium, prevalent in Asia, Northern Australia, and the Indian subcontinent
This study shows that circulating Mucosal-associated invariant T (MAIT) cells are activated, numerically deficient, and functionally impaired in tumor necrosis factor (TNF)-α production in patients with scrub typhus
MAIT cells were defined as CD3+TCRγδ- cells expressing T cell receptor (TCR) Vα7.2 and CD161high (Fig 1A)

Summary

Introduction

Scrub typhus is a mite-borne bacterial infection in humans caused by Orientia tsutsugamushi, an obligate intracellular bacterium, prevalent in Asia, Northern Australia, and the Indian subcontinent. Several studies reported dysfunction of the immunologic response of the host to O. tsutsugamushi; dysregulated levels of certain cytokines, imbalance of Th1/Th2 cytokines and apoptosis of T lymphocytes during acute infection [6,7,8,9]. These findings suggested that the pathogenesis of O. tsutsugamushi infection is related to the virulence of O. tsutsugamushi, and to the host immune response. 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

Objectives

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Results

Conclusion