Alveolar Macrophages and Lung Dendritic Cells Sense RNA and Drive Mucosal IgA Responses

被引:59
作者
Bessa, Juliana [1 ]
Jegerlehner, Andrea [1 ]
Hinton, Heather J. [1 ]
Pumpens, Paul [2 ]
Saudan, Philippe [1 ]
Schneider, Pascal [3 ]
Bachmann, Martin F. [1 ]
机构
[1] Cytos Biotechnol AG, Zurich, Switzerland
[2] Latvian Biomed Res & Study Ctr, Riga, Latvia
[3] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland
关键词
CLASS SWITCH RECOMBINATION; VIRUS-LIKE PARTICLES; B-CELLS; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; T-CELLS; INDUCTION; ABSENCE; PHAGE; TLR9;
D O I
10.4049/jimmunol.0804004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 TGF beta, whereas mucosal IgA production was dependent on Th cells, TACI, and TGF beta. 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. The Journal of Immunology, 2009, 183: 3788-3799.
引用
收藏
页码:3788 / 3799
页数:12
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