期刊
MUCOSAL IMMUNOLOGY
卷 11, 期 1, 页码 82-96出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2017.48
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资金
- Ministry of Education, Culture, Sports, Science, and Technology
- Research program on Emerging and Re-emerging Infection Diseases from Japan Agency for Medical Research and Development (AMED)
- Takeda Science Foundation
- Uehara Memorial Foundation
- Isukura
- Akiyama Life Science Foundation
- Grants-in-Aid for Scientific Research [17K08386, 15K08517, 16K19134] Funding Source: KAKEN
Intranasal inoculation with influenza hemagglutinin subunit with polyinosine-polycytidylic (polyI:C), a synthetic analog for double-stranded RNA, enhances production of vaccine-specific immunoglobulin (Ig) A, which is superior to IgG in prophylactic immunity. The mechanism whereby polyI:C skews to IgA production in the nasal-associated lymph tissue (NALT) was investigated in mouse models. Nasally instilled polyI:C was endocytosed into CD103(+) dendritic cells (DCs) and induced T-cell activation, including interferon (IFN)-gamma production. According to knockout mouse studies, polyI:C activated the Toll-like receptor 3 signal via the adapter TICAM-1 (also called TRIF), that mainly caused T-cell-dependent IgA production. Nasal CD103(+) DCs activated transforming growth factor-beta signaling and activation-induced cytidine deaminase upon polyI:C stimulation. IgA rather than IgG production was impaired in Batf3(-/-) mice, where CD103(+) DCs are defective. Genomic recombination occurred in IgA-producing cells in association with polyI:C-stimulated DCs and nasal microenvironment. PolyI:C induced B-cell-activating factor expression and weakly triggered T-cell-independent IgA production. PolyI:C simultaneously activated mitochondrial antiviral signaling and then type I IFN receptor pathways, which only minimally participated in IgA production. Taken together, CD103(+) DCs in NALT are indispensable for the adjuvant activity of polyI:C in enhancing vaccine-specific IgA induction and protective immunity against influenza viruses.
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