Dustmite proteins meet Immunity: Immunity take advantage of your guest

Asthma affects between 8 to 15% of people in the U.S., and is typically triggered by dust mites, tree and grass pollens and other allergens. Researchers suspect that this inappropriate immune triggering happens when the immune system mistakes allergens (which are otherwise harmless) for pieces of bacteria or other infectious agents. However, the molecular mechanisms underlying this misidentification haven’t been well understood. Researchers at Johns Hopkins Bloomberg School of Public Health have identified the sequence of molecular events by which house dust mites trigger asthma and allergic rhinitis. The researchers, whose study is published in teh journal Nature Immunology, found that allergy-triggering molecules from dust mites can interact with an immune protein called serum amyloid A1 (SAA1), which is better known as a sentinel against bacteria and other infectious agents. The researchers showed step-by-step how this interaction between mite-molecules and SAA1 triggers an allergic-type immune response in mice.

The findings reveal what may be a significant new pathway by which allergic and inflammatory disorders arise. They also suggest that blocking the pathway could potentially work as a preventive or treatment strategy against asthma and other allergic reactions. In their study, the team zeroed in on SAA1, an immune protein that is found, among other places, in the fluid that lines the airways and other mucosal surfaces. A member of the evolutionarily ancient “innate immune system” of mammals, SAA1 is thought to have evolved as a sentinel or early-responder molecule that, for example, recognizes and helps clear away certain types of bacteria and other infectious agents. The researchers found that exposure to dust-mite proteins (Blo t 13 and Der p 13) causes an asthma-like sensitization of the airways of the control group mice. In contrast, exposure to dust-mite proteins hardly had any effect in mice in which SAA1 was neutralized by antibodies, or in mice whose genes for SAA1 were knocked out.

Further experiments confirmed that SAA1, when it is present, directly binds certain dust-mite allergens called fatty-acid binding proteins, which have structural similarities with proteins found in some bacteria and parasites. This allergen-SAA1 interaction releases SAA1 into its active form, wherein it activates a receptor called FPR2 on airway-lining cells. The airway cells then produce and secrete large quantities of interleukin-33, a cytokine known for its ability to stimulate allergic-type immune responses. Confirming the likely relevance to humans, the researchers found evidence of increased production of SAA1 and FPR2 in nasal airway-lining cells from patients with chronic sinusitis–which is often linked to dust-mite allergens, compared to healthy controls. The researchers suspect that the newly described SAA1-FPR2 allergic pathway may be relevant not only in asthma and hay fever-type disorders but also in atopic dermatitis (eczema) and food allergies.

An exciting possibility is to aplly this knowledge to chronic inflammatory disorders such as rheumatoid arthritis and atherosclerosis. Marsha Wills-Karp, PhD, study senior author and professor of Environmental Health and Chair of the Department of Environmental Health and Engineering, commented: “We think that different allergens take different routes to the activation of interleukin-33 and related allergic responses, and this SAA1-FPR2 route seems to be one that is taken by some dust-mite allergens. We therefore think that the signaling interactions that occur immediately downstream of the mite-proteins’ activation of SAA1 may be good targets for future drugs”. She and her colleagues now plan to investigate why some people develop allergic disorders in which this pathway is hyperactive, while most don’t. They also plan to explore the possibility of blocking this pathway, perhaps at the SAA1-FPR2 interaction, as a way of treating asthma and other allergic disorders.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical BIochemistry.

Scientific references

Smole U et al., Wills-Karp M. Nat Immunol Jul 22; 21(7):756.

Gour N, Lajoie S. Curr Allergy Asthma Rep. 2016; 16(9):65. 

Chen M et al. Immunobiology. 2014 Dec; 219(12):916-23.


Informazioni su Dott. Gianfrancesco Cormaci 2472 Articoli
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry specialty in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it