Conventional type 1 dendritic cells induce TH1, TH1-like follicular helper T cells and regulatory T cells after antigen boost via DEC205 receptor

被引:14
|
作者
Sulczewski, Fernando Bandeira [1 ]
Martino, Larissa Alves [1 ]
Almeida, Bianca da Silva [1 ]
Zaneti, Arthur Baruel [1 ]
Ferreira, Natalia Soares [1 ]
da Silva Amorim, Kelly Nazare [1 ]
Yamamoto, Marcio Massao [1 ]
Apostolico, Juliana de Souza [2 ]
Rosa, Daniela Santoro [2 ,3 ]
Boscardin, Silvia Beatriz [1 ,3 ]
机构
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, Sao Paulo, Brazil
[2] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, Sao Paulo, Brazil
[3] INCT, Inst Invest Imunol Iii, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
antigen targeting; DEC205; DCIR2; dendritic cells; monoclonal antibodies; LCRV VIRULENCE PROTEIN; TRANSCRIPTION FACTOR; IMMUNITY; RESPONSES; MICE; SUBSETS; DEC-205; UNRESPONSIVENESS; ACTIVATION; DELIVERY;
D O I
10.1002/eji.202048694
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Conventional dendritic cells (cDCs) are specialized in antigen presentation. In the mouse spleen, cDCs are classified in cDC1s and cDC2s, and express DEC205 and DCIR2 endocytic receptors, respectively. Monoclonal antibodies (mAbs) alpha DEC205 (alpha DEC) and alpha DCIR2 have been fused to different antigens to deliver them to cDC1s or cDC2s. We immunized mice with alpha DEC and alpha DCIR2 fused to an antigen using Poly(I:C) as adjuvant. The initial immune response was analyzed from days 3 to 6 after the immunization. We also studied the influence of a booster dose. Our results showed that antigen targeting to cDC1s promoted a pro-inflammatory T(H)1 cell response. Antigen targeting to cDC2s induced T(FH)cells, GCs, and plasma cell differentiation. After boost, antigen targeting to cDC1s improved the T(H)1 cell response and induced T(H)1-like T(FH)cells that led to an increase in specific antibody titers and IgG class switch. Additionally, a population of regulatory T cells was also observed. Antigen targeting to cDC2s did not improve the specific antibody response after boost. Our results add new information on the immune response induced after the administration of a booster dose with alpha DEC and alpha DCIR2 fusion mAbs. These results may be useful for vaccine design using recombinant mAbs.
引用
收藏
页码:1895 / 1911
页数:17
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