Complement-mediated immune mechanisms in allergy.

Abstract

Allergic conditions are associated with canonical and non-canonical activation of the complement system leading to the release of several bioactive mediators with inflammatory and immunoregulatory properties that regulate the immune response in response to allergens during the sensitization and/or the effector phase of allergic diseases. Further, immune sensors of complement and regulator proteins of the cascade impact on the development of allergies. These bioactive mediators comprise the small and large cleavage fragments of C3 and C5. Here, we provide an update on the multiple roles of immune sensors, regulators and bioactive mediators of complement in allergic airway diseases, food allergy and anaphylaxis. A particular emphasis is on the anaphylatoxins C3a and C5a and their receptors, which are expressed on many of the effector cells in allergy such as mast cells, eosinophils, basophils, macrophages and neutrophils. Also, we will discuss the multiple pathways, by which the anaphylatoxins initiate and control the development of maladaptive type 2 immunity including their impact on innate lymphoid cell recruitment and activation. Finally, we briefly comment on the potential to therapeutically target the complement system in the different allergic conditions. Canonical and non-canonical cleavage of complement factors C3 and C5 generates C3a, C5a and C5adesArg (C5adR), activating the anaphylatoxin receptors C3aR, C5aR1 and C5aR2. Activation of such receptors on multiple innate immune cells and consecutive activation of Type 2 innate lymphoid cells controls the development of several allergic diseases. This article is protected by copyright. All rights reserved.