Toll-like receptor 3 in nasal CD103+ dendritic cells is involved in immunoglobulin A production.

Abstract:

: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)-γ 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-β 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.

journal_name

Mucosal Immunol

journal_title

Mucosal immunology

authors

Takaki H,Kure S,Oshiumi H,Sakoda Y,Suzuki T,Ainai A,Hasegawa H,Matsumoto M,Seya T

doi

10.1038/mi.2017.48

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

82-96

issue

1

eissn

1933-0219

issn

1935-3456

pii

mi201748

journal_volume

11

pub_type

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