Editors' ChoiceImmunology

Innately Allergenic?

Science Signaling  03 Feb 2009:
Vol. 2, Issue 56, pp. ec42
DOI: 10.1126/scisignal.256ec42

As anyone who has suffered through a hay-fever season can attest, otherwise innocuous proteins can elicit allergenic reactions. Only a small number of airborne proteins typically act as aeroallergens in susceptible individuals, but why this should be remains unclear. Noting that Der p 2, the main house dust mite allergen, is structurally related to MD-2, an extracellular component of the Toll-like receptor (TLR) 4 complex that recognizes bacterial lipopolysaccharide (LPS), Trompette et al. examined the effects of Der p 2 on TLR4-mediated signaling. Transfection of Der p 2 enabled the LPS-dependent production of interleukin 8 (IL-8) in HEK293 cells that expressed TLR4 but not MD-2 and enhanced LPS-dependent production of IL-8 in HEK293 cells expressing both TLR4 and MD-2. Tagged forms of Der p 2 and TLR4 could be coimmunoprecipitated from HEK293 cells; Der p 2 also coimmunoprecipitated with LPS and with the TLR4-MD-2 coreceptor CD14 and promoted the association of TLR4 with MD-2. Der p 2 (associated with very small amounts of LPS) promoted TLR4 signaling in primary antigen-presenting cells; airway sensitization and challenge with Der p 2 and very small amounts of LPS elicited allergic asthma in wild-type mice and mice lacking MD-2, but not in mice lacking TLR4. Thus, the authors propose that the allergenicity of Der p 2 arises from its promotion of TLR4 signaling.

A. Trompette, S. Divanovic, A. Visintin, C. Blanchard, R. S. Hegde, R. Madan, P. S. Thorne, M. Wills-Karp, T. L. Gioannini, J. P. Weiss, C. L. Karp, Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585–588 (2009). [PubMed]