Innate Immune Response to an Environmental Fungus, Alternaria, Facilitates Th2-Type Airway Sensitization to a Bystander Antigen

T. Kobayashi1, K. Iijima1, S. Radhakrishnan2, V. Mehta1, R. Vassallo3, L.R. Pease2, H. Kita1

Author address: 

1 Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic Rochester, Rochester, MN 2 Department of Immunology, Mayo Clinic Rochester, Rochester, MN 3 Division of Pulmonary and Critical Care and Internal Medicine, Mayo Clinic

Abstract: 

RATIONALE: Innate immune responses by dendritic cells (DCs) to bacteria and viruses often facilitate Th1-like acquired immune responses to these microorganisms. Because fungi are ubiquitous and exposure to fungi is implicated in development of allergic diseases, we examined the effects of fungal antigens on airway sensitization to ovalbumin (OVA). METHODS: BALB/c mice were exposed intranasally (i.n.) to OVA in the presence of fungal antigens, including Alternaria Alternata (ALT), Aspergillus Versicolor or Candida Albicans, and then challenged i.n. with OVA. Airway hyperresponsiveness (AHR) to methacholine and airway inflammation were examined. The roles of DCs were studied in vivo and in vitro. RESULTS: ALT potently facilitated airway sensitization to OVA and the development of Th2-type immune responses, including OVA-specific IgE and IgG1 in sera, airway eosinophilia, IL-13 in the lungs, OVA-specific IL-5 and IL-13 production by lymph node (LN) cells, and AHR. Without fungal antigen, OVA sensitization was minimal. In naive mice, ALT facilitated antigen uptake and migration of DCs from the lungs to LNs and increased MHC class II and CD86 expression by DCs. ALT stimulated DC presentation of OVA antigen to DO11.10 splenocytes, increased IL-5 and IL-13 production, and decreased IFN-γ production. CONCLUSIONS: Antigen(s) from the ubiquitous fungus, Alternaria, facilitates Th2-type airway sensitization to bystander antigens by enhancing maturation, migration, and antigen presentation of DCs.
2006

abstract No: 

730

Full conference title: 

2006 American Academy of Allergy, Asthma, and Immunology Annual Meeting
    • AAAAI 2006 (62nd)