Targeting Key Factors Involved in Immune Reactions mediated by Tick Bites to the Carbohydrate alpha-Gal

SCHEME: CORE

CALL: 2017

DOMAIN: BM - Translational Biomedical Research

FIRST NAME: Christiane

LAST NAME: Hilger

INDUSTRY PARTNERSHIP / PPP: No

INDUSTRY / PPP PARTNER:

HOST INSTITUTION: LIH

KEYWORDS: Allergen, galactose-alpha-1,3-galactose, alpha-gal syndrome, carbohydrate, red meat allergy, sensitization, tick

START: 2018-07-01

END:

WEBSITE: https://www.lih.lu

Submitted Abstract

Ticks are considered worldwide as important vectors of animal and human diseases. Most recently, tick bites have emerged as trigger of anaphylactic reactions in humans. In particular, tick bites are considered to induce the generation of specific IgE-antibodies directed at the carbohydrate galactose-a-1,3-galactose (alpha-Gal). These serum IgE-antibodies are associated with a previously unrecognized form of delayed anaphylaxis occurring upon consumption of red meat or innards, the alpha-Gal syndrome.Whereas there is strong evidence that ticks are the sensitizing agents, neither the molecules eliciting sensitization nor the mechanism involved in the generation of Th2 immune responses resulting in the production of specific IgE antibodies directed against alpha-Gal are identified.The objectives of the present proposal are i) analysing the allergenicity of alpha-Gal carrying natural and engineered molecules, ii) the phenotyping of cells implicated in immune responses to alpha-Gal epitopes in healthy, sensitized and recently exposed individuals, iii) the analysis of the sensitizing mechanism in an alpha-1,3-galactosyltransferase deficient mouse by inducing immune reactions to alpha-Gal.The investigation of the sensitizing source, the allergenic molecules involved and the mechanisms underlying the sensitization process will generate basic knowledge on immune responses to carbohydrates and provide new targets for therapeutic intervention.

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