Phenotypic Characterization of Peripheral T Cells and Their Dynamics in Scrub Typhus Patients

Hang-Rae Kim,David H. Walker,Sanguk Kim,Ik-Sang Kim,Nam-Hyuk Cho,Bon-A Cho,Youngho Ko,Myung-Sik Choi,Yeon-Sook Kim

doi:10.1371/journal.pntd.0001789

Abstract

BackgroundScrub typhus, caused by Orientia tsutsugamushi infection, is one of the main causes of febrile illness in the Asia-Pacific region. Although cell-mediated immunity plays an important role in protection, little is known about the phenotypic changes and dynamics of leukocytes in scrub typhus patients.Methodology/Principal FindingsTo reveal the underlying mechanisms of immunological pathogenesis, we extensively analyzed peripheral blood leukocytes, especially T cells, during acute and convalescent phases of infection in human patients and compared with healthy volunteers. We observed neutrophilia and CD4+ T lymphopenia in the acute phase of infection, followed by proliferation of CD8+ T cells during the convalescent phase. Massive T cell apoptosis was detected in the acute phase and preferential increase of CD8+ T cells with activated phenotypes was observed in both acute and convalescent phases, which might be associated or correlated with elevated serum IL-7 and IL-15. Interestingly, peripheral Treg cells were significantly down-regulated throughout the disease course.Conclusions/SignificanceThe remarkable decrease of CD4+ T cells, including Treg cells, during the acute phase of infection may contribute to the loss of immunological memory that are often observed in vaccine studies and recurrent human infection.

Highlights

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection, an obligate intracellular bacterium, following the bite of infected larval mites [1]
It has been estimated that one billion people are at risk and one million new cases arise each year in Asian-pacific region
Massive T cell apoptosis was detected in the acute phase and a preferential increase of CD8+ T cells with activated phenotypes was observed in both acute and convalescent phases

Summary

Introduction

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi infection, an obligate intracellular bacterium, following the bite of infected larval mites [1]. While the disease is confined geographically to the Asia-Pacific region, it has been estimated that one billion people are at risk and one million new cases arise each year in the endemic region [2]. This infectious disease has recently become an important public health issue due to regional outbreaks [3,4] and new emergence [5,6]. It has been suggested that adaptive immune cells, such as CD8+ T cells, may cause injury to vascular endothelial cells, leading to vasculitis or perivascularitis during infections by diverse intracellular pathogens [12,13], little is known about the underlying mechanisms of the pathologic damage observed in scrub typhus patients. Cell-mediated immunity plays an important role in protection, little is known about the phenotypic changes and dynamics of leukocytes in scrub typhus patients

Methods

Results

Discussion

Conclusion