How House Dust Mites Trigger Allergies

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.

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 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 protein 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.

"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," says Marsha Wills-Karp, Ph.D., senior author of the study published in Nature Immunology earlier this week.