Goblet cells dictate viral tropism and pathogenesis in nasal and intestinal mucosae
Abstract
Host determinants are critical for shaping the outcomes of viral mucosal infections and developing effective antiviral strategies. However, the regulatory roles of “nonsusceptible” mucosal cells remain unclear. Here, we show that while swine influenza and porcine epidemic diarrhea (PEDV) viruses infect piglet nasal and intestinal epithelia, each virus establishes efficient infection only in its preferred mucosal niche. Goblet cell activity significantly influences mucosal infection outcomes; increased mucus secretion effectively blocks viral entry, while its reduction facilitates viral dissemination. Notably, PEDV activates acetylcholine-cholinergic receptor muscarinic 3 signaling in submucosal enteric neurons to induce goblet cell-associated antigen passages. This mechanism enables the translocation of intestinal bacteria to the lamina propria in early infection, even when the epithelial barrier remains intact, triggering inflammation and exacerbating mucosal damage. Our findings emphasize the crucial role of goblet cells in controlling viral tropism and their potential as targets for developing effective broad-spectrum antiviral approaches.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (11)
Wenqian Wang
Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University
Wenwen Chao
Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University
Hui Zeng
Department of Chemistry, Shanghai Key Lab of Molecular Catalysis and Innovative Materials, iChEM
Rongfeng Tang
Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University
Ruiling Liu
Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University
Chengcheng Wang
State Key Laboratory of Advanced Fiber Materials, College of Chemistry and Chemical Engineering
Xuan Wu
School of Chemistry and Materials Science
Jiaxin Qi
Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University
Yunlei Cao
Ministry of Education Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University
Yuchen Li
Qian Yang