title: Anisakis pegreffii-induced airway hyperresponsiveness is mediated by gamma interferon in the absence of interleukin-4 receptor alpha responsiveness.
abstract: Infection with the fish parasite Anisakis following exposure to contaminated fish can lead to allergic reactions in humans. The present study examined the immunological mechanisms underlying the development of allergic airway inflammation in mice after different routes of sensitization to Anisakis. Wild-type and interleukin-4 receptor alpha (IL-4Ralpha)-deficient BALB/c mice were sensitized intraperitoneally with live or heat-killed Anisakis larvae or by intranasal administration of an Anisakis extract and were subsequently challenged intranasally with an Anisakis extract. Both routes of sensitization induced IL-4Ralpha-dependent allergic airway responses, whereas allergen-specific antibody responses developed only when mice were sensitized intraperitoneally. Intranasal sensitization induced airway hyperresponsiveness (AHR) in wild-type mice only, showing that AHR was IL-4/IL-13 dependent. Unexpectedly, infection with Anisakis larvae induced AHR in both wild-type and IL-4Ralpha-deficient mice. IL-4Ralpha-independent AHR was mediated by gamma interferon (IFN-gamma), as evidenced by the fact that in vivo neutralization of IFN-gamma abrogated AHR. Together, these results demonstrate that both infection with larvae and inhalational exposure to Anisakis proteins are potent routes of allergic sensitization to Anisakis, explaining food- and work-related allergies in humans. Importantly for diagnosis, allergic airway inflammation can be independent of detectable Anisakis-specific antibodies. Moreover, depending on the route of sensitization, AHR can be induced either by IL-4/IL-13 or by IFN-gamma.
authors.affiliation: Division of Immunology, Institute of Infectious Disease and Molecular Medicine, Health Sciences Faculty, University of Cape Town and International Centre for Genetic Engineering and Biotechnology (ICGEB), 7925 Cape Town, South Africa.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirstein
authors.forename: William G C
authors.initials: WG
authors.lastname: Horsnell
authors.forename: Natalie
authors.initials: N
authors.lastname: Nieuwenhuizen
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Lopata
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D017163:Anisakis / Q000276:immunology*; D000909:Antibodies, Helminth / Q000097:blood; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D007371:Interferon-gamma / Q000502:physiology*; D020381:Interleukin-17 / Q000502:physiology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011956:Receptors, Cell Surface / Q000502:physiology*; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D000485:Allergens; D000909:Antibodies, Helminth; D007371:Interferon-gamma; D020381:Interleukin-17; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit