The researchers, whose study is published in the journal Nature ImmunologyThey found that dust mite allergy-triggering molecules can interact with an immune protein called SAA1, which is better known as a sentinel against bacteria and other infectious agents. They have verified step by step how this interaction between the 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. Also, they suggest that blocking the pathway could work as a preventive or treatment strategy against asthma and other allergic reactions.
“We believe that the signaling interactions that occur immediately after SAA1 activation by mite proteins may be good targets for future medications,” explains study lead author Marsha Wills-Karp, professor of environmental health and chair of the Department. of Health and Environmental Engineering of the Bloomberg School.
Researchers suspect that this inappropriate immune triggering due to mites occurs when the immune system mistakes allergens, which are otherwise harmless, with fragments of bacteria or other infectious agents. However, the molecular mechanisms underlying this misidentification have not been well understood.
In their study, Wills-Karp and colleagues focused on SAA1, an immune protein 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 believed to have evolved as a sentinel or early-response molecule that, for example, recognizes and helps kill certain types of bacteria and other infectious agents.
The researchers found that exposure to dust mite proteins causes asthma-like sensitization of the airways of mice in the control group. In contrast, exposure to dust mite proteins had little effect in mice in which SAA1 was neutralized by antibodies, or in mice whose genes for SAA1 were killed.
Other experiments confirmed that SAA1, when present, binds directly to certain dust mite allergens called fatty acid binding proteins, which have structural similarities to the proteins found in some bacteria and parasites.
This allergen-SAA1 interaction releases SAA1 in its active form, in which it activates a receptor called FPR2 in the cells that line the airways. Cells in the airways produce and secrete large amounts 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 cells lining the nasal airways of patients with chronic sinusitis, which is often related to dust mite allergens, compared to healthy controls.
“We believe that different allergens take different pathways for interleukin-33 activation and related allergic responses, and this SAA1-FPR2 route appears to be the pathway taken by some dust mite allergens,” says Wills-Karp.
The team now plans to investigate why some people develop allergic disorders in which this pathway is hyperactive, while most do not. They also aim to explore the possibility of blocking this pathway, perhaps in the SAA1-FPR2 interaction, as a way to treat asthma and other allergic disorders.
The researchers suspect that the recently described SAA1-FPR2 allergic pathway may be relevant not only in asthma-like disorders and hay fever, but also in atopic dermatitis (eczema) and food allergies, possibly even in chronic inflammatory disorders such as rheumatoid arthritis and atherosclerosis.
–
