TGEV infection up-regulates FcRn expression via activation of NF-κB signaling.

Jinyue Guo,Qigai He,Fei Li,Shaoju Qian,Shaowen Li,Rui Luo,Hui Jin,Zili Li,Dingren Bi,Xianrong Meng

doi:10.1038/srep32154

Abstract

It has been well characterized that the neonatal Fc receptor (FcRn) transports maternal IgG to a fetus or newborn and protects IgG from degradation. We previously reported that FcRn is expressed in a model of normal porcine intestinal epithelial cells (IPEC-J2). Transmissible gastroenteritis is an acute enteric disease of swine that is caused by transmissible gastroenteritis virus (TGEV). How porcine FcRn (pFcRn) expression is regulated by pathogenic infection remains unknown. Our research shows that IPEC-J2 cells infected with TGEV had up-regulated pFcRn expression. In addition, the NF-κB signaling pathway was activated in IPEC-J2 cells by TGEV infection. Furthermore, treatment of TGEV-infected IPEC-J2 cells with the NF-κB-specific inhibitor BAY 11-7082 resulted in down-regulation of pFcRn expression. Transient transfection of pFcRn promoter luciferase report plasmids with overexpression of NF-κB p65 transcription factor enhanced the activation of the luciferase report plasmids. We identified four NF-κB transcription factor binding sites in the promoter region of this gene using luciferase reporter system, chromatin immunoprecipitation, electromobility shift assay, and supershift analysis. Together, the data provide the first evidence that TGEV infection up-regulates pFcRn expression via activation of NF-κB signaling.

Highlights

Immunoglobulin G is a major Ig isotype in mucosal secretions and is involved in host defense
Our studies showed that porcine FcRn (pFcRn) expression can be triggered by Transmissible gastroenteritis virus (TGEV) infection, through Nuclear factor-κB (NF-κB) signal activation
To determine whether TGEV is capable of modulating pFcRn expression in IPEC-J2 cells, infectious TGEV or UV-inactivated virus was adsorbed to confluent monolayers of IPEC-J2 cells at an multiplicity of infection (MOI) of 1 and pFcRn mRNA was measured 8, 12, 24, 30, 36 and 48 h post-virus exposure by real-time RT-PCR

Summary

Introduction

Immunoglobulin G is a major Ig isotype in mucosal secretions and is involved in host defense. Some researchers have reported FcRn overexpression by Tg modification in mice and rabbits prolongs the IgG half-life and enhances the humoral immune response of these animals[17,18,19]. These Tg animals displayed significantly larger spleens containing a higher number of Ag-specific B cells and plasma cells in response to immunization, increased antibody diversity and prolonged Ag-specific IgG half-life[20]. These findings suggest that TGEV infection induces a number of changes in host-cell biology that could influence cells function

Methods

Results

Conclusion