TIPE2 negatively regulates mycoplasma pneumonia-triggered immune response via MAPK signaling pathway

Yuanyuan Zhang,Qingqing Wang,Shufen Mei,Ting Pan,Dehua Yang,Zhimin Chen,Yunlian Zhou

doi:10.1038/s41598-017-13825-y

Abstract

Excessive immune responses played an important role in pathophysiology of mycoplasma pneumonia (MP) infection. Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) is a negative regulator of immune response. This study investigated the expression change of TIPE2 and its role in immune defense against MP infection, as well as the underlying mechanisms. Expressions of TIPE2 both in patients and in macrophages in vitro after MP infection were measured. We further studied cytokine production and mitogen-activated protein kinase (MAPK) signaling function in macrophages with interfered expression of TIPE2 upon MP infection. A significant decrease of TIPE2 mRNA expression was observed in peripheral blood mononuclear cells (PBMCs) from MP patients, which was correlated with the severity of infection. Accordingly we found down-regulation of TIPE2 expression in macrophages after MP infection. In vitro study further suggested that TIPE2 jeopardized inflammatory cytokine production trigged by MP infection via inhibiting MAPK signaling pathway. These findings provided evidences of the novel function of TIPE2 in anti-MP immunity and its possible clinical utility related clinical significance.

Highlights

Mycoplasma pneumoniae (MP), an atypical bacterium, is a common pathogenetic organism of respiratory infection in children[1,2]
To investigate whether Tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) played a role in human defense against mycoplasma pneumonia (MP) infection, we collected the peripheral blood samples from 180 pediatric Mycoplasma pneumoniae pneumonia (MPP) cases admitted to our hospital, and 60 healthy children as the control
The expression of TIPE2 mRNA in peripheral blood mononuclear cells (PBMCs) was significantly decreased in MP patient groups than healthy controls, and was much lower in refractory cases (Fig. 1), indicating that the expression of TIPE2 in PBMCs might have a correlation with the anti-MP immune response of the host

Summary

Introduction

Mycoplasma pneumoniae (MP), an atypical bacterium, is a common pathogenetic organism of respiratory infection in children[1,2]. TIPE2 deficiency in mice leads to fetal inflammatory diseases, and abnormal expression of TIPE2 in humans was found to be associated with infectious diseases and autoimmune disorders, such as hepatitis B, systemic lupus erythematosus, asthma, and experimental stroke[17,18,19,20]. To date, it is unclear whether TIPE2 plays a role in regulation of immunity against MP infection. In this study, we first investigated the expression of TIPE2 both in vivo (in patients with MPP) and vitro (in macrophages after MP infection), and identify the potential effects of TIPE2 on MP-triggered immune response in vitro

Methods

Results

Conclusion