Microorganism-induced suppression of allergic airway disease: novel therapies on the horizon?

Abstract

Allergic airway disease is a major global health burden, and novel treatment options are urgently needed. Numerous epidemiological and experimental studies suggest that certain helminths and bacteria protect against respiratory allergies. These microorganisms are strong regulators of the immune system, and various potential regulatory mechanisms by which they protect against allergic airway inflammation have been proposed. Whereas early studies addressed the beneficial effect of natural infections, the focus now shifts toward identifying the dominant protective molecules and exploring their efficacy in models of allergic airway disease. In this article, we will review the evidence for microbe-mediated protection from allergic airway disease, the potential modes of action involved and discuss advances as well as limitations in the translation of this knowledge into novel treatment strategies against allergic airway disease.

Keywords::

• alternatively activated macrophages
• asthma
• bacteria
• dendritic cells
• gut microbiota
• helminths
• immunomodulation
• parasite
• respiratory allergies
• regulatory B cells
• regultory T cell

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Atopic disease (e.g., allergic rhinitis, allergic asthma) is a major global health burden today. Medication options are limited and only alleviate the symptoms, therefore novel treatment options need to be developed urgently.

• Helminths/microbiota modulate the host immune system, suppressing the immune response to themselves and bystander antigens such as allergens. The ‘hygiene hypothesis’ suggests that the drastic increase in incidence rates for atopic disease can be ascribed to a reduction in infectious pressure and the resulting imbalance of the immune system.

• A body of epidemiological evidence underpins that helminths (e.g., hookworms, schistosomes) and certain bacteria (e.g., Helicobacter pylori) protect against allergic asthma in humans.

• In vivo studies suggest mechanisms by which microorganisms or their products protect against allergic airway disease, including shifting of the Th1/Th2 immune balance, induction of Treg/regulatory B cells, modulation of dendritic cell/macrophage function and impairment of chemotaxis and effector cell (e.g., mast cell, basophil) function.

• Helminth- and microbial-derived molecules have been identified that efficiently protect against experimental allergic airway inflammation and that include whole antigen preparations, excretory-secretory products and single molecules (single/recombinant) of helminths as well as live-attenuated and freeze-dried bacteria, bacterial lysates and single bacterial molecules.

• At the moment microbial-derived treatments, including probiotics, are not routinely applied in the clinics to treat allergic airway disease. While working toward a novel treatment option for atopic patients based on microbial-derived molecules, a range of factors such as safety, mode of action (general vs antigen-specific tolerance), timing and route of administration need to be taken into account.

• We expect that more immune suppressive molecules will be described and that these molecules will further progress into clinical trials.

Notes