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

Epithelial TLR expression plays an important role in the innate and adaptive immune responses. NF-κB is a branch of the downstream signaling pathways of TLR and RLR, which also play important roles in various immune responses. Diverse coronaviruses can escape host immune responses via NF-κB activation through different pathways. PEDV activates NF-κB signaling through TLRs, while mouse hepatitis virus (MHV) does so through RLRs (Li et al., 2010; Cao et al., 2015a) . IPEC-J2 cells express mRNA encoding TLR1, TLR2, TLR3, TLR4, TLR6, TLR8, TLR9, TLR10 , IL-1α, IL-6, IL-7, IL-8, IL-18, TNFα, and GM-CSF (Bowie and Haga, 2005; Burkey et al., 2009; Mariani et al., 2009) . Rotavirus infection triggers the production of IL-8, IL-6, and TNF-α in IECs by activating the TLR3 and RIG-I pathways (Broquet et al., 2011) . Compared with the NC siRNA, TLR3-, TLR9-, RIG-, MyD88-, and TRIF-specific siRNAs inhibited TGEV-induced FcRn activation, while TLR2-, TLR4-, and TLR8-specific siRNAs did not. We speculate that TGEV activates NF-κB via the TLR3, TLR9, and RIG-I pathways. Our results suggest that TLR3, TLR9, and RIG-I may be used to activate the FcRn signaling pathway when TGEV infects IPEC-J2 cells. Recently, our research has shown that PEDV down-regulate the NF-κB signaling pathway to inhibit FcRn by TLR3 and RIG-I pathway in the early stage of infected piglets (Qian et al., 2019) . PEDV and PDCoV N protein inhibited IFN-β by RIG-I pathway (Ding et al., 2014b; Likai et al., 2019) , and we found that TGEV N protein up-regulated FcRn by RIG-I pathway. Moreover, TGEV infection induced IFN-β production and PEDV inhibited IFN-β production Cao et al., 2015b) . These results may be important causes of PEDV being more pathogenic than TGEV.