Toll-like receptors (TLRs) are essential components of innate immunity and provide defensive inflammatory responses to invading pathogens. Located within the plasma membranes of cells and also intracellular endosomes, TLRs can detect a range of
pathogen associated molecular patterns from bacteria, viruses and fungi. TLR activation on dendritic cells can propagate to an adaptive immune response, making them attractive targets for the development of both prophylactic and therapeutic
vaccines. In contrast to conventional adjuvants such as
aluminium salts,
TLR agonists have a clear immunomodulatory profile that favours
anti-allergic T lymphocyte responses. Consequently, the potential use of TLRs as adjuvants in Allergen Immunotherapy (AIT) for
allergic rhinitis and
asthma remains of great interest.
Allergic Rhinitis is a Th2-driven,
IgE-mediated disease that occurs in atopic individuals in response to exposure to otherwise harmless aeroallergens such as pollens, house dust mite and animal dander. AIT is indicated in subjects with
allergic rhinitis whose symptoms are inadequately controlled by
antihistamines and nasal
corticosteroids. Unlike
anti-allergic drugs, AIT is disease-modifying and may induce long-term disease remission through mechanisms involving upregulation of
IgG and
IgG4 antibodies, induction of regulatory T and B cells, and immune deviation in favour of Th1 responses that are maintained
after treatment discontinuation. This process takes up to three years however, highlighting an unmet need for a more efficacious
therapy with faster onset. Agonists targeting different TLRs to treat
allergy are at different stages of development. Synthetic TLR4, and TLR9 agonists have progressed to clinical trials, while TLR2, TLR5 and TLR7 agonists been shown to have potent
anti-allergic effects in human in vitro experiments and in vivo in animal studies. The
anti-allergic properties of TLRs are broadly characterised by a combination of enhanced Th1 deviation, regulatory responses, and induction of
blocking antibodies. While promising, a durable effect in larger clinical trials is yet to be observed and further long-term studies and comparative trials with conventional AIT are required before TLR adjuvants can be considered for inclusion in AIT. Here we critically evaluate experimental and clinical studies investigating TLRs and discuss their potential role in the future of AIT.