Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo

Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regu...

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Main Authors: Ricardo W. Alberca Custodio, Luciana Mirotti, Eliane Gomes, Fernanda P.B. Nunes, Raquel S. Vieira, Luís Graça, Rafael R. Almeida, Niels O. S. Câmara, Momtchilo Russo
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/10/1165
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author Ricardo W. Alberca Custodio
Luciana Mirotti
Eliane Gomes
Fernanda P.B. Nunes
Raquel S. Vieira
Luís Graça
Rafael R. Almeida
Niels O. S. Câmara
Momtchilo Russo
author_facet Ricardo W. Alberca Custodio
Luciana Mirotti
Eliane Gomes
Fernanda P.B. Nunes
Raquel S. Vieira
Luís Graça
Rafael R. Almeida
Niels O. S. Câmara
Momtchilo Russo
author_sort Ricardo W. Alberca Custodio
collection DOAJ
description Elevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required <i>MyD88</i>-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a <i>MyD88</i>-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.
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spelling doaj.art-e7f309d3295347c5a7bead74e8daa34a2023-09-02T18:34:07ZengMDPI AGCells2073-44092019-09-01810116510.3390/cells8101165cells8101165Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In VivoRicardo W. Alberca Custodio0Luciana Mirotti1Eliane Gomes2Fernanda P.B. Nunes3Raquel S. Vieira4Luís Graça5Rafael R. Almeida6Niels O. S. Câmara7Momtchilo Russo8Institute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Molecular Medicine, University of Lisbon, 1649-028 Lisbon, PortugalInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilInstitute of Biomedical Sciences, Department of Immunology, University of Sao Paulo, Sao Paulo 05508-000, BrazilElevated levels of immunoglobulin E (IgE) are associated with allergies and other immunological disorders. Sensitization with alum adjuvant favours IgE production while CpG-ODN adjuvant, a synthetic toll-like receptor 9 (TLR9) agonist, inhibits it. The cellular mechanisms underlying in vivo TLR regulation of immunoglobulin production, specially IgE, are still controversial. Specifically, TLR-mediated IgE regulation in vivo is not yet known. In this study we showed that augmented levels of IgE induced by sensitizations to OVA with or without alum adjuvant or with OVA-pulsed dendritic cells (DCs) were inhibited by co-administration of CpG. Notably, CpG-mediated suppression of IgE production required <i>MyD88</i>-expression on DCs but not on B-cells. This finding contrasts with previous in vitro studies reporting regulation of IgE by a direct action of CpG on B cells via MyD88 pathway. In addition, we showed that CpG also inhibited IgE production in a <i>MyD88</i>-dependent manner when sensitization was performed with OVA-pulsed DCs. Finally, CpG signalling through MyD88 pathway was also necessary and sufficient to prevent anaphylactic antibody production involved in active cutaneous anaphylaxis.https://www.mdpi.com/2073-4409/8/10/1165allergyigeigg2canaphylaxisdendritic cells
spellingShingle Ricardo W. Alberca Custodio
Luciana Mirotti
Eliane Gomes
Fernanda P.B. Nunes
Raquel S. Vieira
Luís Graça
Rafael R. Almeida
Niels O. S. Câmara
Momtchilo Russo
Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
Cells
allergy
ige
igg2c
anaphylaxis
dendritic cells
title Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
title_full Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
title_fullStr Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
title_full_unstemmed Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
title_short Dendritic Cells Expressing MyD88 Molecule Are Necessary and Sufficient for CpG-Mediated Inhibition of IgE Production In Vivo
title_sort dendritic cells expressing myd88 molecule are necessary and sufficient for cpg mediated inhibition of ige production in vivo
topic allergy
ige
igg2c
anaphylaxis
dendritic cells
url https://www.mdpi.com/2073-4409/8/10/1165
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