Activation of Mast Cells Is Essential for Development of House Dust Mite Dermatophagoides farinae-Induced Allergic Airway Inflammation in Mice

Abstract

In this study, we demonstrate that Dermatophagoides farinae (Der f), a major source of airborne allergens, but not OVA, could rapidly activate mast cells in mice. This was indicated by an elevation of serum mouse mast cell protease 1, a mast cell-specific proteinase, as early as 30 min after intratracheal challenge. Administration of sodium cromoglycate (40 mg/kg, i.p., 1 h before Der f instillation), a mast cell stabilizer, not only suppressed acute mouse mast cell protease 1 production but also attenuated the allergic airway inflammation provoked by repetitive Der f challenge in mice (five times at 1-wk interval). Der f induced the expression of mRNA for TNF-α, IL-1β, IL-4, IL-6, IL-9, and IL-13 in mastocytoma P815 cells and stimulated both P815 cells and bone marrow-derived mast cells to produce IL-4, IL-6, and TNF-α in a dose- and time-dependent manner. Cycloheximide as well as sodium cromoglycate blocked the Der f-induced IL-4 production, indicating a de novo protein synthesis process. Supernatants of Der f-stimulated mast cells chemoattracted monocytes and T lymphocytes; they up-regulated the expression of costimulatory B7 molecules, eotaxin, RANTES, monocyte chemoattractant protein 1, and IFN-inducible protein 10 mRNA of alveolar macrophages; they supported PHA-induced T cell proliferation; and they promoted Th2 cell development. Our data indicate that mast cells may be an important cell type during the initiation of Der f sensitization in the airway by modulating the function of alveolar macrophages and T cells.

TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment

“…77,78 Transgenic overexpression of IP10 in epithelial cells reportedly leads to increased accumulation of CD8 ϩ cells in the lungs in murine models of asthma. 79 RANTES, MIP-1␤, and IP10, chemokines that have been shown to contribute to the recruitment of T cells in various pathologic settings, [79][80][81] are induced on protein or mRNA level in BMMCs stimulated with poly(I:C) and NDV. Normal antiviral host responses require CD8 ϩ T cells to migrate to sites of virus infection, where they recognize and kill infected cells.…”

CD1d-Independent Developmental Acquisition of Prompt IL-4 Gene Inducibility in Thymus CD161(NK1)−CD44lowCD4+CD8− T Cells Is Associated with Complementarity Determining Region 3-Diverse and Biased Vβ2/Vβ7/Vβ8/Vα3.2 T Cell Receptor Usage

“…It has recently been shown that alum activates a previously unidentified myeloid cell to expresses IL-4 (97). Also, allergens, such as Der f, have been shown to directly activate IL-4 expression in mast cells (98). It is possible that allergens in general possess certain structural similarities that can activate IL-4 expression in innate cells of the immune system (e.g., the two examples given above), thus providing IL-4 required for the development of naive T cells into Th2/Tc2 effectors.…”

Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to FcεRI-mediated activation

“…Rodent and huMC are known to express antigen-presenting molecules such as MHC-II [13][14][15] and CD80 (B7-1) [16]. Moreover, mouse mast cells are known to present intracellular antigens to T cells [17,18].…”