Protective immune mechanisms of Yifei Tongluo, a Chinese herb formulation, in the treatment of mycobacterial infection.

Xin Fan,Ning Li,Xiaoshuang Wang,Meiyi Xu,Beinan Wang,Jingyu Zhang,Xueting Liu,Horacio Bach

doi:10.1371/journal.pone.0203678

Abstract

Yifei Tongluo (YFTL) is a traditional Chinese medicine (TCM) formulation which has been shown clinical efficacy in treatment of patients with multidrug-resistant tuberculosis in China. However, the underlying mechanisms of the effects of YFTL are lacking. This study investigated the effects of YFTL on immune regulation with a mouse lung infection model with Bacille Calmette-Guérin (BCG). We found that compared with untreated mice, the lung mycobacterial load in YFTL-treated mice was significantly reduced, accompanied by alleviated pulmonary inflammation with reduction of pro-inflammatory cytokines and increase of prostaglandin E2 (PGE2). Flow cytometry analyses showed that Th1 cells were significantly higher in the lungs of YFTL-treated mice at early infection time. The results suggest that YFTL-treatment down-regulates pulmonary inflammation, which facilitates a rapid infiltration of Th1 cells into the lungs. Moreover, the Th1 cells in the lungs were resolved faster at later time concomitant with increased the regulatory T cells (Tregs). The reduction of mycobacterial burden associated with improved tissue pathology, faster Th1 cell trafficking, and accelerated resolution of Th1 cells in the lungs of YFTL-treated mice indicates that YFTL improves mycobacterial clearance by maintaining lung homeostasis and dynamically regulating T cells in the lung parenchyma, and suggests that YFTL can be used as host-directed therapies that target immune responses to mycobacterial infection.

Highlights

Mycobacterium tuberculosis (Mtb) is a major health problem worldwide that causes mortality of almost 2 million persons per year [1]
We employed a Bacille Calmette-Guerin (BCG) infection model and demonstrate that Yifei Tongluo (YFTL), a clinically effective traditional Chinese medicine (TCM) formulation used in the treatment of TB patients, improves outcomes of BCG infected mice by regulating host immune responses, leading to increased eradication of the bacteria
The results reveal that the beneficial effects of YFTL on mycobacterial infection are due to its ability to suppress early inflammation in the lungs through Prostaglandin E2 (PGE2) production and to regulate the dynamics of Th1 cell numbers in the lung parenchyma

Summary

Introduction

Mycobacterium tuberculosis (Mtb) is a major health problem worldwide that causes mortality of almost 2 million persons per year [1]. The susceptibility to the onset and progression of TB is the pathogenic destruction of infected tissue but the outcome of host immune response to the pathogen. Inflammation caused by a wide array of inflammatory cytokines in response to infection dictates the eventual pathology of TB by contributing to early host immune defense and initiating an adaptive immune response, such as activation and recruitment of Th1 cells to the infected site for successful control of TB [2]. Protective immune mechanisms of Yifei Tongluo in the treatment of mycobacterial infection

Objectives

Methods

Results

Conclusion