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Differential TLR ‐induced cytokine production by human mast cells is amplified by Fcɛ RI triggering
Author(s) -
Suurmond J.,
Dorjée A. L.,
Knol E. F.,
Huizinga T. W. J.,
Toes R. E. M.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12509
Subject(s) - degranulation , immunoglobulin e , cytokine , immunology , mast cell , allergic inflammation , allergy , receptor , flow cytometry , interleukin 33 , chemistry , biology , interleukin , antibody , biochemistry
Summary Background Mast cells are mainly present in strategic locations, where they may have a role in defence against parasites and bacteria. These pathogens can be recognized by mast cells via Toll‐like receptors ( TLR ). Allergic symptoms are often increased in the presence of pathogens at the site of allergen exposure, but it is unknown which cytokines can mediate such an effect. Objective To study whether an interaction between IgE‐ and TLR ‐mediated activation of human mast cells can contribute to exacerbated inflammatory responses. Methods Peripheral blood‐derived mast cells were stimulated with TLR ligands, in the presence or absence of anti‐IgE triggering, after which degranulation was measured using flow cytometry and cytokine production was evaluated by multiplex assays, and ELISA . For evaluation of allergen‐specific responses, mast cells were sensitized with serum of allergic individuals or controls, after which they were stimulated using allergens in combination with TLR ligands. Results Simultaneous triggering of mast cells via IgE and TLR ligands greatly enhanced cytokine production but not IgE‐induced degranulation. Different TLR ligands specifically enhanced the differential production of cytokines in conjunction with Fcε RI triggering. Importantly, only TLR ‐4 and TLR ‐6 were able to induce robust production of IL ‐13, an important molecule in allergic reactions. Conclusions & Clinical Relevance These results indicate that the simultaneous presence of pathogen‐ or danger‐associated signals and Fcε RI triggering via specific IgE can significantly modify mast cell‐mediated allergic reactions via synergistic production of cytokines and inflammatory mediators and provide an explanation of augmented allergic symptoms during infection.