Abstract
Acanthamoeba is a free-living amoeba commonly present in the environment and often found in human airway cavities. Acanthamoeba possesses strong proteases that can elicit allergic airway inflammation. To our knowledge, the aeroallergenicity of Acanthamoeba has not been reported. We repeatedly inoculated mice with Acanthamoeba trophozoites or excretory-secretory (ES) proteins intra-nasally and evaluated symptoms and airway immune responses. Acanthamoeba trophozoites or ES proteins elicited immune responses in mice that resembled allergic airway inflammation. ES proteins had strong protease activity and activated the expression of several chemokine genes (CCL11, CCL17, CCL22, TSLP, and IL-25) in mouse lung epithelial cells. The serine protease inhibitor phenyl-methane-sulfonyl fluoride (PMSF) inhibited ES protein activity. ES proteins also stimulated dendritic cells and enhanced the differentiation of naive T cells into IL-4-secreting T cells. After repeated inoculation of the protease-activated receptor 2 knockout mouse with ES proteins, airway inflammation and Th2 immune responses were markedly reduced, but not to basal levels. Furthermore, asthma patients had higher Acanthamoeba-specific IgE titers than healthy controls and we found Acanthamoeba specific antigen from house dust in typical living room. Our findings suggest that Acanthamoeba elicits allergic airway symptoms in mice via a protease allergen. In addition, it is possible that Acanthamoeba may be one of the triggers human airway allergic disease.
Highlights
An airway allergic reaction is characterized by the synthesis of allergen-specific immunoglobulin (Ig) E and Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, which lead to the recruitment and sensitization of effector cells such as eosinophils, basophils, and mast cells [1]
Treatment with Acanthamoeba trophozoites elicits strong allergic airway inflammation To demonstrate the effects of Acanthamoeba on allergic airway inflammation, we introduced Acanthamoeba trophozoites (56104) into the airways of mice and assessed biological and pathological changes (Figure 1A)
The levels of IL-4, -5, and 13 (Th2 cytokines) in bronchoalveolar lavage fluid (BALF) and in the culture medium of lung-draining lymph nodes (LLNs) T cells increased in the Acanthamoeba-infected group, compared with levels in the control group (Figure S1B)
Summary
An airway allergic reaction is characterized by the synthesis of allergen-specific immunoglobulin (Ig) E and Th2 cytokines, such as interleukin (IL)-4, IL-5, and IL-13, which lead to the recruitment and sensitization of effector cells such as eosinophils, basophils, and mast cells [1]. Antigen recognition and uptake by innate immune cells is the first step in the process of antigen presentation, which can lead to the initiation of the adaptive immune response [2]. Many allergens exhibit intrinsic protease activities, and some proteases from infectious agents, parasites, and fungi have been identified as potent allergens [4,5,6,7,8]. These protease allergens induce Th2 immune reactions by activating several chemokines and cytokines [8]. Protease activities may be critical to the initiation of allergic responses
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