title: Asthma-related environmental fungus, Alternaria, activates dendritic cells and produces potent Th2 adjuvant activity.
abstract: Asthma is thought to result from dysregulated Th2-like airway inflammatory responses to the environment. Although the etiology of asthma is not fully understood in humans, clinical and epidemiological evidence suggest a potential link between exposure to environmental fungi, such as Alternaria, and development and/or exacerbation of asthma. The goal of this project was to investigate the mechanisms of airway Th2 responses by using Alternaria as a clinically relevant model for environmental exposure. Airway exposure of naive animals to an experimental Ag, OVA, or a common allergen, short ragweed pollen, induced no or minimal immune responses to these Ags. In contrast, mice developed strong Th2-like immune responses when they were exposed to these Ags in the presence of Alternaria extract. Extracts of other fungi, such as Aspergillus and Candida, showed similar Th2 adjuvant effects, albeit not as potently. Alternaria stimulated bone marrow-derived dendritic cells (DCs) to express MHC class II and costimulatory molecules, including OX40 ligand, in vitro. Importantly, Alternaria inhibited IL-12 production by activated DCs, and DCs exposed to Alternaria enhanced Th2 polarization of CD4(+) T cells. Furthermore, adoptive airway transfer of DCs, which had been pulsed with OVA in the presence of Alternaria, showed that the recipient mice had enhanced IgE Ab production and Th2-like airway responses to OVA. Thus, the asthma-related environmental fungus Alternaria produces potent Th2-like adjuvant effects in the airways. Such immunogenic properties of certain environmental fungi may explain their strong relationships with human asthma and allergic diseases.
authors.affiliation: Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Takao
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Koji
authors.initials: K
authors.lastname: Iijima
authors.forename: Suresh
authors.initials: S
authors.lastname: Radhakrishnan
authors.forename: Vinay
authors.initials: V
authors.lastname: Mehta
authors.forename: Robert
authors.initials: R
authors.lastname: Vassallo
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Lawrence
authors.forename: Jong-Chol
authors.initials: JC
authors.lastname: Cyong
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
authors.forename: Katsuji
authors.initials: K
authors.lastname: Oguchi
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology*; D000528:Alternaria / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000382:microbiology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011058:Pollen / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000485:Allergens; D016207:Cytokines; D010047:Ovalbumin