CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens Targeted to CD8 alpha(+) and CD8 alpha(-) Conventional Dendritic Cell Subsets

Autor(es)

Antonialli, Renan ^[1] ; Sulczewski, Fernando Bandeira ^[1] ; da Silva Amorim, Kelly Nazare ^[1] ; Almeida, Bianca da Silva ^[1] ; Ferreira, Natalia Soares ^[1] ; Yamamoto, Marcio Massao ^[1] ; Soares, Irene Silva ^[2] ; de Souza Ferreira, Luis Carlos ^[3] ; Rosa, Daniela Santoro ^{[4, 5]} ; Boscardin, Silvia Beatriz ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[5] INCT, III, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 8, DEC 4 2017.
• Citações Web of Science: 8

Resumo

Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets through the use of hybrid monoclonal antibodies (mAbs) to DC surface receptors fused to antigens of interest opened new perspectives for the induction of robust immune responses. Normally, the hybrid mAbs are administered with adjuvants that induce DC maturation. In this work, we targeted an antigen to the CD8 alpha(+) or the CD8 alpha(-) DC subsets in the presence of CpG oligodeoxinucleotides (ODN) or bacterial flagellin, using hybrid alpha DEC205 or alpha DCIR2 mAbs, respectively. We also accessed the role of toll-like receptors (TLRs) 5 and 9 signaling in the induction of specific humoral and cellular immune responses. Wild-type and TLR5 or TLR9 knockout mice were immunized with two doses of the hybrid alpha DEC205 or alpha DCIR2 mAbs, as well as with an isotype control, together with CpG ODN 1826 or flagellin. A chimeric antigen containing the Plasmodium vivax 19 kDa portion of the merozoite surface protein (MSP1(19)) linked to the Pan-allelic DR epitope was fused to each mAb. Specific CD4(+) T cell proliferation, cytokine, and antibody production were analyzed. We found that CpG ODN 1826 or flagellin were able to induce CD4(+) T cell proliferation, CD4(+) T cells producing pro-inflammatory cytokines, and specific antibodies when the antigen was targeted to the CD8 alpha(+) DC subset. On the other hand, antigen targeting to CD8 alpha(-) DC subset promoted specific antibody responses and proliferation, but no detectable pro-inflammatory CD4(+) T cell responses. Also, specific antibody responses after antigen targeting to CD8 alpha(+) or CD8 alpha(-) DCs were reduced in the absence of TLR9 or TLR5 signaling, while CD4(+) T cell proliferation was mainly affected after antigen targeting to CD8 alpha(+) DCs and in the absence of TLR9 signaling. These results extend our understanding of the modulation of specific immune responses induced by antigen targeting to DCs in the presence of different adjuvants. Such knowledge may be useful for the optimization of DC-based vaccines. (AU)

• Processo FAPESP: 14/50631-0 - Imagem e aperfeiçoamento da proteção imunológica contra parasitas da malária
• Beneficiário: Silvia Beatriz Boscardin
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/11442-4 - Estudo dos mecanismos protetores induzidos pela vacinação de camundongos com anticorpos de fusão capazes de direcionar proteínas do vírus da dengue para células dendríticas
• Beneficiário: Silvia Beatriz Boscardin
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/18874-2 - Mecanismo de Geração de Resposta Imune Humoral Induzida pelo Direcionamento do Antígeno MSP1(19)PADRE para Duas Populações Distintas de Células Dendríticas via Receptores DEC205 e DCIR2
• Beneficiário: Fernando Bandeira Sulczewski
• Modalidade de apoio: Bolsas no Brasil - Mestrado