Transmissible Gastroenteritis Virus Infection Up-Regulates FcRn Expression via Nucleocapsid Protein and Secretion of TGF-ß in Porcine Intestinal Epithelial Cells

Qian, Shaoju; Gao, Zitong; Cao, Rui; Yang, Kang; Cui, Yijie; Li, Shaowen; Meng, Xianrong; He, Qigai; Li, Zili

In the innate immune system, PRRs recognize pathogenassociated molecular patterns (PAMPs) as the first step in the host's resistance to infection. After recognition of PAMPs, these receptors interact with their corresponding binding molecules to trigger downstream signaling events that activate NF-κB and IFN regulatory factors that induce several types of antiviral cytokines (Thompson and Locarnini, 2007) . TGEV infection activates transcriptional activator 1 (JAK-STAT1) signaling pathways according to a quantitative proteomics study in PK-15 cells . TGEV infection has been reported to activate the mitogen-activated protein kinase (MAPK) pathway and destroy epithelial barrier integrity in IPEC-J2 cells (Zhao et al., 2014) . TGEV N, nsp2 and nsp14 proteins all induce NF-κB activation (Zhou et al., 2017; Wang et al., 2018; Zhang et al., 2018) , but the regulatory mechanism of FcRn is still unknown. Most studies on TGEV have focused on the induction and activation of NF-κB and IFN, but host cell biology may affect cell function. However, the detailed mucosal immunity mechanism during TGEV pathogenesis remains unknown. Viral invasion always triggers an inflammatory response, which is the key mediator of host response to microbial pathogens (McDonnell et al., 2016) . TGEV infection has been shown to induce the production of IFNs and pro-inflammatory cytokines in vitro and in vivo (Cruz et al., 2013) . A direct correlation between dsRNA antiviral response induction and TGEV virulence has been demonstrated (Cruz et al., 2011) . Moreover, the inflammatory factors produced will also contribute to the production of a strong immune response. TNF-α and IL-1β can activate NF-κB to up-regulate the expression of human FcRn, which enhances FcRn-mediated IgG transport (Liu et al., 2007) . TGEV infection was also found to induce EMT via TGFβ in IPEC-J2 cells (Xia et al., 2017) . The aim of this study was to identify the TGEV-encoded proteins involved in inducing FcRn production.