Functions of Exosomes and Microbial Extracellular Vesicles in Allergy and Contact and Delayed-Type Hypersensitivity

Abstract

Extracellular vesicles, such as exosomes, are newly recognized intercellular conveyors of functional molecular mechanisms. Notably, they transfer RNAs and proteins between different cells that can then participate in the complex pathogenesis of allergic and related hypersensitivity responses and disease mechanisms, as described herein. This review highlights this important new appreciation of the in vivo participation of such extracellular vesicles in the interactions between allergy-mediating cells. We take into account paracrine epigenetic exchanges mediated by surrounding stromal cells and the endocrine receipt of exosomes from distant cells via the circulation. Exosomes are natural ancient nanoparticles of life. They are made by all cells and in some form by all species down to fungi and bacteria, and are present in all fluids. Besides a new focus on their role in the transmission of genetic regulation, exosome transfer of allergens was recently shown to induce allergic inflammation. Importantly, regulatory and tolerogenic exosomes can potently inhibit allergy and hypersensitivity responses, usually acting nonspecifically, but can also proceed in an antigen-specific manner due to the coating of the exosome surface with antibodies. Deep analysis of processes mediated by exosomes should result in the development of early diagnostic biomarkers, as well as allergen-specific, preventive and therapeutic strategies. These will likely significantly diminish the risks of current allergen-specific parenteral desensitization procedures, and of the use of systemic immunosuppressive drugs. Since extracellular vesicles are physiological, they can be fashioned for the specific delivery of therapeutic molecular instructions through easily tolerated, noninvasive routes, such as oral ingestion, nasal administration, and perhaps even inhalation.

Syngeneic red blood cell–induced extracellular vesicles suppress delayed‐type hypersensitivity to self‐antigens in mice

“…Furthermore, while boosting of mice with OVA in the presence of various adjuvants triggers cytotoxic T cell responses and the production of antibodies, 28 epicutaneous sensitization with hapten alone or intradermal immunization with OVA without an adjuvant induces CHS or DTH reactions, respectively. 9,12,29 Finally, our current observations demonstrate that intradermal administration of sMRBC mixed with OVA-coupled sMRBC also induces a DTH reaction and that both hapten-induced CHS and DTH to self-erythrocytes could be antigen-specifically suppressed by intravenous administration of a high dose of intact sMRBC. Thus, the herein presented research findings contribute to our understanding of erythrocyte-induced immune tolerance by characterizing the underlying biological mechanism involving EVs that target APCs to ultimately suppress effector T cells.…”

“…In contrast, in our conditions, freshly collected sMRBC deprived of buffy coat were used as a plain DPBS suspension. Furthermore, while boosting of mice with OVA in the presence of various adjuvants triggers cytotoxic T cell responses and the production of antibodies, epicutaneous sensitization with hapten alone or intradermal immunization with OVA without an adjuvant induces CHS or DTH reactions, respectively . Finally, our current observations demonstrate that intradermal administration of sMRBC mixed with OVA‐coupled sMRBC also induces a DTH reaction and that both hapten‐induced CHS and DTH to self‐erythrocytes could be antigen‐specifically suppressed by intravenous administration of a high dose of intact sMRBC.…”

“…Naive or sMRBC‐tolerized mice were actively contact sensitized and 5 days later challenged with picryl chloride (PCL, Chemtronix) as described elsewhere . After 24 hours, ear swelling was measured with an engineer's micrometre (Mitutoyo) by a blinded observer .…”

“…Along these lines, recent findings revealed that intravenous administration of a high dose of syngeneic mouse red blood cells (sMRBC) coupled with hapten or protein antigen induces CD8 + suppressor T (Ts) cells in mice . These regulatory cells inhibit contact (CHS) or delayed‐type hypersensitivity (DTH) reactions by releasing miRNA‐150‐carrying extracellular vesicles (EVs), further coated with B1 cell–derived, antigen‐specific antibody free light chains (LCs) . It is worth noting that surface expression of LCs confers antigen specificity of tolerance mediated by EV‐carried miRNA‐150 .…”

Staphylococcus aureus‐derived extracellular vesicles induce monocyte recruitment by activating human dermal microvascular endothelial cells in vitro

“…[12][13][14][15] In particular, the application of S. aureus-derived EVs (SEVs) to tape-stripped mouse skin resulted in AD-like inflammation in the absence of live bacterial cells. 12,16,17 Moreover, SEV-specific IgE serum levels were significantly increased in patients with AD, 12 suggesting that SEVs can evoke immune responses and promote AD; however, the molecular mechanism underlying SEV-mediated inflammatory responses remains unclear.…”