
Vol. 164, No. 1, 2014
Issue release date: June 2014

Editor's Choice -- Free Access

Int Arch Allergy Immunol 2014;164:46-63 (DOI:10.1159/000362553)

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A New Era of Targeting the Ancient Gatekeepers of the Immune System: Toll-Like Agonists in the Treatment of Allergic Rhinitis and Asthma

Aryan Z.a · Holgate S.T.c · Radzioch D.e · Rezaei N.a,b,d

aMolecular Immunology Research Center and Department of Immunology, School of Medicine and bResearch Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; cFaculty of Medicine, Clinical and Experimental Sciences, Southampton General Hospital, Southampton, anddDepartment of Infection and Immunity, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, UK; eDepartment of Medicine and Department of Human Genetics, McGill University, Montreal, Que., Canada

Corresponding Author

Abstract

Toll-like receptors (TLR) belong to a large family of pattern recognition receptors known as the ancient ‘gatekeepers' of the immune system. TLRs are located at the first line of defense against invading pathogens as well as aeroallergens, making them interesting targets to modulate the natural history of respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or prophylactic preparations useful for asthma/allergic rhinitis (AR) patients. MPL® (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9 agonist, show strong immunogenicity effects that make them appropriate adjuvants for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific allergen immunotherapy, currently the only available ‘curative' treatment for respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so far reported with such compounds targeting TLRs, with the most common adverse effects being transient and local irritation (e.g. redness, swelling and pruritus). Many other compounds that target TLRs have been found to suppress airway inflammation, eosinophilia and airway hyper-responsiveness in various animal models of allergic inflammation. Indeed, in the future a wide variability of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are likely to emerge.

Outline