Publication Date:
2008-12-09
Description:
Aeroallergy results from maladaptive immune responses to ubiquitous, otherwise innocuous environmental proteins. Although the proteins targeted by aeroallergic responses represent a tiny fraction of the airborne proteins humans are exposed to, allergenicity is a quite public phenomenon-the same proteins typically behave as aeroallergens across the human population. Why particular proteins tend to act as allergens in susceptible hosts is a fundamental mechanistic question that remains largely unanswered. The main house-dust-mite allergen, Der p 2, has structural homology with MD-2 (also known as LY96), the lipopolysaccharide (LPS)-binding component of the Toll-like receptor (TLR) 4 signalling complex. Here we show that Der p 2 also has functional homology, facilitating signalling through direct interactions with the TLR4 complex, and reconstituting LPS-driven TLR4 signalling in the absence of MD-2. Mirroring this, airway sensitization and challenge with Der p 2 led to experimental allergic asthma in wild type and MD-2-deficient, but not TLR4-deficient, mice. Our results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties. The fact that other members of the MD-2-like lipid-binding family are allergens, and that most defined major allergens are thought to be lipid-binding proteins, suggests that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843411/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843411/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trompette, Aurelien -- Divanovic, Senad -- Visintin, Alberto -- Blanchard, Carine -- Hegde, Rashmi S -- Madan, Rajat -- Thorne, Peter S -- Wills-Karp, Marsha -- Gioannini, Theresa L -- Weiss, Jerry P -- Karp, Christopher L -- R01 AI075159/AI/NIAID NIH HHS/ -- R01 AI075159-01/AI/NIAID NIH HHS/ -- R01 EY014648/EY/NEI NIH HHS/ -- R01 HL067736/HL/NHLBI NIH HHS/ -- R01 HL067736-05/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Jan 29;457(7229):585-8. doi: 10.1038/nature07548. Epub 2008 Dec 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19060881" target="_blank"〉PubMed〈/a〉
Keywords:
Air
;
Allergens/chemistry/genetics/*immunology/*metabolism
;
Animals
;
Antigens, Dermatophagoides/chemistry/genetics/*immunology/*metabolism
;
Arthropod Proteins
;
Asthma/genetics/immunology
;
Cell Line
;
Disease Models, Animal
;
Female
;
Humans
;
Lipopolysaccharides/immunology
;
Lymphocyte Antigen 96/chemistry/deficiency/genetics/immunology/metabolism
;
Mice
;
Molecular Mimicry/*immunology
;
Protein Binding
;
Toll-Like Receptor 4/deficiency/genetics/*immunology/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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