Anisakis pegreffii-induced airway hyperresponsiveness is mediated by gamma interferon in the absence of interleukin-4 receptor alpha responsiveness

Kirstein, Frank, Horsnell, William G. C., Nieuwenhuizen, Natalie, Ryffel, Bernhard, Lopata, Andreas L., and Brombacher, Frank (2010) Anisakis pegreffii-induced airway hyperresponsiveness is mediated by gamma interferon in the absence of interleukin-4 receptor alpha responsiveness. Infection and Immunity, 78 (9). pp. 4077-4086.

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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-4R{alpha})-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-4R{alpha}-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-4R{alpha}-deficient mice. IL-4R{alpha}-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}.

Item ID: 15064
Item Type: Article (Refereed Research - C1)
ISSN: 1098-5522
Date Deposited: 30 Nov 2010 01:55
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060199 Biochemistry and Cell Biology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
Citation Count from Web of Science Web of Science 6
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