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Review
. 2020 Jun 30:11:1334.
doi: 10.3389/fimmu.2020.01334. eCollection 2020.

Mechanisms of Particles in Sensitization, Effector Function and Therapy of Allergic Disease

Affiliations
Review

Mechanisms of Particles in Sensitization, Effector Function and Therapy of Allergic Disease

Isabella Anna Joubert et al. Front Immunol. .

Erratum in

Abstract

Humans have always been in contact with natural airborne particles from many sources including biologic particulate matter (PM) which can exhibit allergenic properties. With industrialization, anthropogenic and combustion-derived particles have become a major fraction. Currently, an ever-growing number of diverse and innovative materials containing engineered nanoparticles (NPs) are being developed with great expectations in technology and medicine. Nanomaterials have entered everyday products including cosmetics, textiles, electronics, sports equipment, as well as food, and food packaging. As part of natural evolution humans have adapted to the exposure to particulate matter, aiming to protect the individual's integrity and health. At the respiratory barrier, complications can arise, when allergic sensitization and pulmonary diseases occur in response to particle exposure. Particulate matter in the form of plant pollen, dust mites feces, animal dander, but also aerosols arising from industrial processes in occupational settings including diverse mixtures thereof can exert such effects. This review article gives an overview of the allergic immune response and addresses specifically the mechanisms of particulates in the context of allergic sensitization, effector function and therapy. In regard of the first theme (i), an overview on exposure to particulates and the functionalities of the relevant immune cells involved in allergic sensitization as well as their interactions in innate and adaptive responses are described. As relevant for human disease, we aim to outline (ii) the potential effector mechanisms that lead to the aggravation of an ongoing immune deviation (such as asthma, chronic obstructive pulmonary disease, etc.) by inhaled particulates, including NPs. Even though adverse effects can be exerted by (nano)particles, leading to allergic sensitization, and the exacerbation of allergic symptoms, promising potential has been shown for their use in (iii) therapeutic approaches of allergic disease, for example as adjuvants. Hence, allergen-specific immunotherapy (AIT) is introduced and the role of adjuvants such as alum as well as the current understanding of their mechanisms of action is reviewed. Finally, future prospects of nanomedicines in allergy treatment are described, which involve modern platform technologies combining immunomodulatory effects at several (immuno-)functional levels.

Keywords: adjuvants; alum; animal dander; house dust mite feces; immunomodulation; mold spores; nanomedicine; pollen.

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Figures

Figure 1
Figure 1
Overview on sources, targets and impact of particulates in allergic sensitization.
Figure 2
Figure 2
Mechanisms of allergic sensitization. DCs located in the epithelia of peripheral tissues are exposed to allergens, immunomodulatory compounds and particulate matter (PM). Once activated, highly specialized CD11b+/CD301+/PDL2+/KFL4+/IRF4+ DCs migrate into the lymph nodes to initiate the Th2 differentiation program. Upon exposure to epithelial-derived factors (IL-25, thymic stromal lymphopoietin (TSLP) and IL-33), group 2 innate lymphoid cells (ILC2) produce Th2 cytokines. This further promotes Th2 cell polarization and leads to exacerbation of the allergic response characterized by the secretion of IgE by B cells, and the activation of MCs and eosinophils. Basophils act as antigen-presenting cells (APCs) by presenting DC-derived antigenic peptides to T cells via a specific membrane transfer mechanism called trogocytosis.
Figure 3
Figure 3
Mechanisms of allergen-specific immunotherapy. Tregs produce cytokines such as IL-10 and TFG-β, which have the potential to suppress Th2 responses. Upon induction of tolerogenic DCs Th1 are mobilized at the expense of Th2 cells. They produce IFN-γ and stimulate the production of IgG4 and IgA antibodies by means of class switching. IgG4 antibodies can block allergen-induced MCs, basophils and eosinophils and hence, limit allergic symptoms by decreasing mediator release (178, 179).
Figure 4
Figure 4
Dendritic cell-targeting by different nanoparticles. Novel approaches intend to increase immunogenicity (green arrow in box) and decrease allergenicity (red arrow in box) of the nano-fromulated vaccines (i.e., virus-like NPs, copolymer, and peptide-based polymeric NPs and carbohydrate NPs) taken up by DCs through receptor-mediated phagocytosis. Allergen encapsulation and increased uptake shall render vaccines hypoallergenic (i.e., inhibition of MC degranulation, red arrow in box) and more immunogenic (green arrow in box), hence, improving the overall efficacy of AIT.

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