Allergens as immunomodulatory proteins: the cat dander protein Fel d 1 enhances TLR activation by lipid ligands

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J Immunol. Author manuscript; available in PMC Feb 15, 2014.

Published in final edited form as:

J Immunol. Aug 15, 2013; 191(4): 10.4049/jimmunol.1300284.

Published online Jul 22, 2013. doi:  10.4049/jimmunol.1300284

PMCID: PMC3836235

EMSID: EMS53686

Jurgen Herre,1,2 Hans Grönlund,3 Heather Brooks,2 Lee Hopkins,2 Lisa Waggoner,4 Ben Murton,5 Monique Gangloff,5Olaniyi Opaleye,5 Edwin R. Chilvers,1 Kate Fitzgerald,4 Nick Gay,5 Tom Monie,5,* and Clare Bryant*

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Abstract

Allergic responses can be triggered by structurally diverse allergens. Most allergens are proteins yet extensive research has not revealed how they initiate the allergic response and why the myriad of other inhaled proteins do not. Amongst these allergens, the cat secretoglobulin protein Fel d 1, is the major allergen and responsible for severe allergic responses. In this study we show that like the mite dust allergen Der p 2, Fel d 1 substantially enhances signalling through the innate receptors TLR4 and TLR2. In contrast to Der p 2 however, Fel d 1 does not act by mimicking the TLR4 co-receptor MD2 and is not able to bind stably to the TLR4/MD2 complex in vitro. Fel d 1 does however, bind to the TLR4 agonist lipopolysaccharide, suggesting that a lipid transfer mechanism may be involved in the Fel d 1 enhancement of TLR signalling. We also show that the dog allergen Can f 6, a member of a distinct class of lipocalin allergens, has very similar properties to Fel d 1. We propose that Fel d 1 and Can f 6 belong to a group of allergen immunomodulatory proteins (IMPs) that enhance innate immune signalling and promote airway hypersensitivity reactions in diseases such as asthma.

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Abstract

Allergic responses can be triggered by structurally diverse allergens. Most allergens are proteins yet extensive research has not revealed how they initiate the allergic response and why the myriad of other inhaled proteins do not. Amongst these allergens, the cat secretoglobulin protein Fel d 1, is the major allergen and responsible for severe allergic responses. In this study we show that like the mite dust allergen Der p 2, Fel d 1 substantially enhances signalling through the innate receptors TLR4 and TLR2. In contrast to Der p 2 however, Fel d 1 does not act by mimicking the TLR4 co-receptor MD2 and is not able to bind stably to the TLR4/MD2 complex in vitro