Immature lung TNFR2- conventional DC 2 subpopulation activates moDCs to promote cyclic di-GMP mucosal adjuvant responses in vivo.
Mucosal Immunol
; 12(1): 277-289, 2019 01.
Article
in En
| MEDLINE
| ID: mdl-30327534
ABSTRACT
Cyclic dinucleotides (CDNs), including cyclic di-GMP (CDG), are promising vaccine adjuvants in preclinical/clinical trials. The in vivo mechanisms of CDNs are not clear. Here we investigated the roles of lung DC subsets in promoting CDG mucosal adjuvant responses in vivo. Using genetically modified mice and adoptive cell transfer, we identified lung conventional DC 2 (cDC2) as the central player in CDG mucosal responses. We further identified two functionally distinct lung cDC2 subpopulations TNFR2+pRelB+ and TNFR2-pRelB- cDC2. The TNFR2+ cDC2 were mature and migratory upon intranasal CDG administration while the TNFR2- cDC2 were activated but not mature. Adoptive cell transfer showed that TNFR2- cDC2 mediate the antibody responses of CDG, while the TNFR2+ cDC2 generate Th1/17 responses. Mechanistically, immature TNFR2- cDC2 activate monocyte-derived DCs (moDCs), which do not take up intranasally administered CDG. moDCs promote CDG-induced generation of T follicular helper- and germinal center B cells in the lungs. Our data revealed a previously undescribed in vivo mode of DCs action, whereby an immature lung TNFR2- cDC2 subpopulation directs the non-migratory moDCs to generate CDG mucosal responses in the lung.
Full text:
1
Database:
MEDLINE
Main subject:
Dendritic Cells
/
Cyclic GMP
/
Th1 Cells
/
Receptors, Tumor Necrosis Factor, Type II
/
Th17 Cells
/
Lung
/
Mucous Membrane
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Mucosal Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2019
Type:
Article
Affiliation country:
United States