title: Acanthamoeba protease activity promotes allergic airway inflammation via protease-activated receptor 2.
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.
authors.affiliation: Department of Parasitology, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Immunoregulatory therapeutics group in Brain Busan 21 project, Busan, Republic of Korea.
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Park
authors.affiliation: Department of Parasitology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Cho
authors.affiliation: Department of Parasitology, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Immunoregulatory therapeutics group in Brain Busan 21 project, Busan, Republic of Korea.
authors.forename: Shin Ae
authors.initials: SA
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Hye-Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: Department of Nursing, College of Nursing, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Parasitology, School of Medicine, Pusan National University, Yangsan, Republic of Korea; Immunoregulatory therapeutics group in Brain Busan 21 project, Busan, Republic of Korea.
authors.forename: Hak Sun
authors.initials: HS
authors.lastname: Yu
mesh_terms: D000048:Acanthamoeba / Q000201:enzymology* / Q000276:immunology; D000562:Amebiasis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018925:Chemokines; D044464:Receptor, PAR-2; D007073:Immunoglobulin E; D010447:Peptide Hydrolases