Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity
Volaluck Supajatura, … , Chisei Ra, Hideoki Ogawa
Volaluck Supajatura, … , Chisei Ra, Hideoki Ogawa
Published May 15, 2002
Citation Information: J Clin Invest. 2002;109(10):1351-1359. https://doi.org/10.1172/JCI14704.
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Article Immunology

Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity

Abstract

Toll-like receptor 2 (TLR2) and TLR4 play important roles in the early innate immune response to microbial challenge. To clarify the functional roles of TLRs 2 and 4 in mast cells, we examined bone marrow–derived mast cells (BMMCs) from TLR2 or TLR4 gene-targeted mice. Peptidoglycan (PGN) from Staphylococcus aureus stimulated mast cells in a TLR2-dependent manner to produce TNF-α, IL-4, IL-5, IL-6, and IL-13, but not IL-1β. In contrast, LPS from Escherichia coli stimulated mast cells in a TLR4-dependent manner to produce TNF-α, IL-1β, IL-6, and IL-13, but not IL-4 nor IL-5. Furthermore, TLR2- but not TLR4-dependent mast cell stimulation resulted in mast cell degranulation and Ca2+ mobilization. In a mast cell–dependent model of acute sepsis, TLR4 deficiency of BMMCs in mice resulted in significantly higher mortality because of defective neutrophil recruitment and production of proinflammatory cytokines in the peritoneal cavity. Intradermal injection of PGN led to increased vasodilatation and inflammation through TLR2-dependent activation of mast cells in the skin. Taken together, these results suggest that direct activation of mast cells via TLR2 or TLR4 by respective microligands contributes to innate and allergic immune responses.

Authors

Volaluck Supajatura, Hiroko Ushio, Atsuhito Nakao, Shizuo Akira, Ko Okumura, Chisei Ra, Hideoki Ogawa

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Figure 1

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PGN but not LPS induces mast cell degranulation and Ca2+ mobilization th...
PGN but not LPS induces mast cell degranulation and Ca2+ mobilization through TLR2. (a) BMMCs from TLR2+/+ (white bars), TLR2–/– (black bars), TLR4+/+ (light gray bars), and TLR4–/– (dark gray bars) were incubated with indicated concentrations of PGN or LPS. β-Hexosaminidase in the supernatant was measured as described in Methods. Data shown are mean ± SD of three experiments conducted with different BMMC preparations. BMMCs stimulated with IgE and anti-IgE or PMA and ionomycin were used as positive control. (b) TLR2+/+ and TLR2–/– BMMCs were stimulated with 100 μg/ml of PGN; then Ca2+ mobilization was evaluated as described in Methods. BMMCs stimulated with IgE and anti-IgE were used as positive control. Data shown is one representative result from several experiments that had similar results.