PMID- 29255470
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 8
DP  - 2017
TI  - CpG Oligodeoxinucleotides and Flagellin Modulate the Immune Response to Antigens 
      Targeted to CD8alpha(+) and CD8alpha(-) Conventional Dendritic Cell Subsets.
PG  - 1727
LID - 10.3389/fimmu.2017.01727 [doi]
LID - 1727
AB  - 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 CD8alpha(+) or the 
      CD8alpha(-) DC subsets in the presence of CpG oligodeoxinucleotides (ODN) or 
      bacterial flagellin, using hybrid alphaDEC205 or alphaDCIR2 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 alphaDEC205 or 
      alphaDCIR2 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 CD8alpha(+) 
      DC subset. On the other hand, antigen targeting to CD8alpha(-) 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 CD8alpha(+) or CD8alpha(-) DCs were reduced in the absence of TLR9 or TLR5 
      signaling, while CD4(+) T cell proliferation was mainly affected after antigen 
      targeting to CD8alpha(+) 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.
FAU - Antonialli, Renan
AU  - Antonialli R
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Sulczewski, Fernando Bandeira
AU  - Sulczewski FB
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Amorim, Kelly Nazare da Silva
AU  - Amorim KNDS
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Almeida, Bianca da Silva
AU  - Almeida BDS
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Ferreira, Natalia Soares
AU  - Ferreira NS
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Yamamoto, Marcio Massao
AU  - Yamamoto MM
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Soares, Irene Silva
AU  - Soares IS
AD  - Department of Clinical and Toxicological Analysis, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo, Brazil.
FAU - Ferreira, Luis Carlos de Souza
AU  - Ferreira LCS
AD  - Department of Microbiology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
FAU - Rosa, Daniela Santoro
AU  - Rosa DS
AD  - Department of Microbiology, Immunology and Parasitology, Federal University of 
      Sao Paulo, Sao Paulo, Brazil.
AD  - Institute for Investigation in Immunology (iii), INCT, Sao Paulo, Brazil.
FAU - Boscardin, Silvia Beatriz
AU  - Boscardin SB
AD  - Department of Parasitology, Institute of Biomedical Sciences, University of Sao 
      Paulo, Sao Paulo, Brazil.
AD  - Institute for Investigation in Immunology (iii), INCT, Sao Paulo, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20171204
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC5723008
OTO - NOTNLM
OT  - CpG oligodeoxinucleotides 1826
OT  - antigen targeting
OT  - dendritic cells
OT  - flagellin
OT  - hybrid monoclonal antibodies
EDAT- 2017/12/20 06:00
MHDA- 2017/12/20 06:01
PMCR- 2017/01/01
CRDT- 2017/12/20 06:00
PHST- 2017/08/10 00:00 [received]
PHST- 2017/11/22 00:00 [accepted]
PHST- 2017/12/20 06:00 [entrez]
PHST- 2017/12/20 06:00 [pubmed]
PHST- 2017/12/20 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2017.01727 [doi]
PST - epublish
SO  - Front Immunol. 2017 Dec 4;8:1727. doi: 10.3389/fimmu.2017.01727. eCollection 
      2017.