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

Ricardo W Alberca Custodio,Fernanda P.B Nunes,Niels O S Câmara,Rafael R Almeida,Raquel S Vieira,Luís Graça,Luciana Mirotti,Momtchilo Russo,Eliane Gomes

doi:10.3390/cells8101165

Ricardo W Alberca Custodio, Fernanda P.B Nunes + Show 7 more

Open Access

https://doi.org/10.3390/cells8101165

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Journal: Cells	Publication Date: Sep 28, 2019
Citations: 10	License type: CC BY 4.0

Affiliation: Universidade de São Paulo, University of Lisbon

Abstract

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 MyD88-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 MyD88-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.

Highlights

Over the past five decades the prevalence and incidence of allergic disease have increased worldwide
We show that addition of CpG to OVA/alum suppressed immunoglobulin E (IgE) production and increased IgG2c production in mice selectively deleted for MyD88 molecule in B cells but not in dendritic cells (DCs) indicating, that MyD88-expressing DCs are necessary and sufficient to suppress IgE and to enhance IgG2c production induced by sensitization with CpG-containing adjuvant formulation
We found that independently of whether alum adjuvant was used for OVA sensitization, addition of CpG to OVA resulted in inhibition of

Summary

Introduction

Over the past five decades the prevalence and incidence of allergic disease have increased worldwide. Atopy is a term used to describe a group of diseases such as allergic rhinitis, hay fever, asthma, atopic eczema and food allergy in individuals that develop an immediate immunoglobulin. E (IgE)-mediated hypersensitivity to otherwise harmless environmental antigens [1]. The work of Shirakawa et al showing a strong inverse association between serum levels of IgE and delayed type hypersensitivity to Mycobacterium tuberculosis antigens among Japanese schoolchildren [2] lend support to the “hygiene hypothesis” that postulated an inverse relationship between allergy and infections [3]. IgE and IgG1 antibody switching is mediated by interleukin-4 (IL-4)-producing T helper 2 (Th2) cells while interferon gamma (IFNγ)-producing Th1 cells favour IgG2a switching [5]. It is expected that Toll-like receptors (TLRs) agonists that are viewed as Th1 adjuvants would induce Th1-associated isotypes while alum, that is considered a

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