Inhibition of FceRI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes

Nature Medicine (2007) 13:1375-1381.

Speaker: 魏麗勳                                                     Time:14:00-15:00, Apr. 23, 2008

Commentator: 胥直利 老師                                   Room:601

    Allergy is characterized by elevated titers of IgE antibodies, which bind to high-affinity Fce�n receptor (FceRI) on mast cells and trigger their degranulation to release inflammatory mediators. High titers of serum IgE are also observed in helminth infection that selectively induces strong Th2 type immune responses (1). However, in developing countries, the frequent increase of IgE in helminth infection does not actually enhance the prevalence of allergic diseases (2), raising a possibility that helminth infection can protect people from these inflammatory disorders. ES-62 is a filarial nematode-secreted, phosphorylcholine-containing glycoprotein that exerts multiple immunomodulatory functions (3). In this paper the authors found that ES-62 is able to inhibit FceRI-induced degranulation and cytokine production of mast cells, by blocking phospholipase D (PLD)-mediated Ca²⁺ mobilization and NF-kB activation. These inhibitory effects result from association between ES-62 and TLR-4, which sequesters PKC-a, a key mediator linking FceRI to PLD and mast cell degranulation. Moreover, in mouse models of mast cell-dependent hypersensitivity in skin and lung, ES-62 can also inhibit the allergic responses. Therefore, the authors not only reveal a new mechanism for the protective effect of parasitic infection from allergy, but also indicate a potential approach to treat allergy.

Reference:

(1)   Anthony RM. et al., Protective immune mechanisms in helminth infection.

Nature Reviews Immunolog (2007) 7: 975-985.

(2)   Yazdanbakhsh M et al., Allergy, Parasites, and the Hygiene Hypothesis. Science (2002) 296: 490-494.

(3)   Goodridge HS. et al., Signalling mechanisms underlying subversion of the immune response by the filarial nematode secreted product ES-62. Immunology, (2005) 115: 296–304.