Alveolar macrophages and lung dendritic cells sense RNA and drive mucosal IgA responses.
The mechanisms regulating systemic and mucosal IgA responses in the respiratory tract are incompletely understood. Using virus-like particles loaded with single-stranded RNA as a ligand for TLR7, we found that systemic vs mucosal IgA responses in mice were differently regulated. Systemic IgA responses following s.c. immunization were T cell independent and did not require TACI or TGFbeta, whereas mucosal IgA production was dependent on Th cells, TACI, and TGFbeta. Strikingly, both responses required TLR7 signaling, but systemic IgA depended upon TLR7 signaling directly to B cells whereas mucosal IgA required TLR7 signaling to lung dendritic cells and alveolar macrophages. Our data show that IgA switching is controlled differently according to the cell type receiving TLR signals. This knowledge should facilitate the development of IgA-inducing vaccines.
Bessa
Juliana
J
Cytos Biotechnology AG, Zürich-Schlieren, Switzerland.
Jegerlehner
Andrea
A
Hinton
Heather J
HJ
Pumpens
Paul
P
Saudan
Philippe
P
Schneider
Pascal
P
Bachmann
Martin F
MF
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008562:Membrane Glycoproteins; D051379:Mice; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology*; D012313:RNA / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer; D051199:Toll-Like Receptor 7; D016212:Transforming Growth Factor beta; D053303:Transmembrane Activator and CAML Interactor Protein
D007070:Immunoglobulin A; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; C486361:Tnfrsf13b protein, mouse; D051199:Toll-Like Receptor 7; D016212:Transforming Growth Factor beta; D053303:Transmembrane Activator and CAML Interactor Protein; D012313:RNA