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

Author(s)

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]}

Affiliation

^[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

• Document type: Journal article
• Source: European Journal of Immunology; v. 50, n. 12 JUL 2020.
• Web of Science Citations: 1

Abstract

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. (AU)

• FAPESP's process: 18/20821-2 - Analysis of interleucin 10 influence in cellular and humoral responses promoted by antigen targeting to the CD8a+DEC205+ dendritic cells
• Grantee: Larissa Alves Martino
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/18874-2 - Mechanism of Generation of humoral immune response induced by targeting of MSP1(19)-PADRE antigen to two different subsets of dendritic cells via DEC205 and DCIR2 receptors
• Grantee: Fernando Bandeira Sulczewski
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 17/06503-5 - Analysis of the humoral response induced by Dengue and Zika virus infection using recombinant proteins from the envelope of these viruses
• Grantee: Arthur Baruel Zaneti
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/16565-2 - Evaluation of humoral and cellular immune responses induced by targeting the domain III of the dengue virus envelope protein to the DEC205+ dendritic cell subpopulation.
• Grantee: Bianca da Silva Almeida
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/00145-2 - Influence of STAT1, STAT3, STAT5 and STAT6 signaling pathways on conventional dendritic cells in the instruction of auxiliary T cell response
• Grantee: Fernando Bandeira Sulczewski
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/07142-9 - Influence of STAT1, STAT3, STAT5 and STAT6 Signaling Pathways on Conventional Dendritic Cells in the Instruction of the T-Cell Auxiliary Response
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants