title: CpG DNA assists the whole inactivated H9N2 influenza virus in crossing the intestinal epithelial barriers via transepithelial uptake of dendritic cell dendrites.
abstract: Intestinal mucosa remains a pivotal barrier for the oral vaccine absorption of H9N2 whole inactivated influenza virus (WIV). However, CpG DNA, as an adjuvant, can effectively improve relevant mucosal and systemic immunity. The downstream mechanism is well confirmed, yet the evidence of CpG DNA assisting H9N2 WIV in transepithelial delivery is lacking. Here, we reported both in vitro and in vivo that CpG DNA combined with H9N2 WIV was capable of recruiting additional dendritic cells (DCs) to the intestinal epithelial cells (ECs) to form transepithelial dendrites (TEDs) for luminal viral uptake. Both CD103(+) and CD103(-) DCs participated in this process. The engagement of the chemokine CCL20 from the apical ECs and the DCs drove DC recruitment and TED formation. Virus-loaded CD103(+) but not CD103(-) DCs also quickly migrated into mesenteric lymph nodes within 2 h. Moreover, the mechanism of CpG DNA was independent of epithelial transcytosis and disruption of the epithelial barriers. Finally, the subsequent phenotypic and functional maturation of DCs was also enhanced. Our findings indicated that CpG DNA improved the delivery of H9N2 WIV via TEDs of intestinal DCs, and this may be an important mechanism for downstream effective antigen-specific immune responses.
authors.affiliation: Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Qin
authors.affiliation: Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Key Lab of Animal Physiology and Biochemistry, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D054418:Chemokine CCL20 / Q000235:genetics / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010641:Phenotype; D057900:Transcytosis; D057705:Transendothelial and Transepithelial Migration / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D054418:Chemokine CCL20; D009838:Oligodeoxyribonucleotides