Mast cells are thought to participate in a variety of immune responses, such as parasite resistance and the allergic reaction. Mast cell development depends on stem cell factor (Kit ligand) and its receptor, c-Kit. Gab2 is an adaptor molecule containing a pleckstrin homology domain and potential binding sites for SH2 and SH3 domains. Gab2 is phosphorylated on tyrosine after stimulation with cytokines and growth factors, including KitL. Gab2-deficient mice were created to define the physiological requirement for Gab2 in KitL/c-Kit signaling and mast cell development. In Gab2-deficient mice, the number of mast cells was reduced markedly in the stomach and less severely in the skin. Bone marrow-derived mast cells (BM-MCs IntroductionMast cells are hematopoietic-lineage cells that participate in immunoglobulin (Ig)E-associated immune responses, including allergic reactions and parasite resistance (see Galli 1 for a review). It was recently shown that mast cells also participate in the innate immunity to bacterial infection, in which IgE may not be involved. 2 Genetic evidence indicates that Kit ligand (KitL) and its receptor, c-Kit, play essential roles in mast cell development. Mutations in the mouse Kit ligand and c-Kit genes (Steel and White spotting) lead to defects in the development of melanocytes, germ cells, erythroid cells, basophils, and mast cells. 3-5 c-Kit is a receptor-type tyrosine kinase that displays some homology with platelet-derived growth factor receptors. The binding of KitL to c-Kit induces the dimerization and transphosphorylation of c-Kit. Tyrosyl-phosphorylated c-Kit recruits signaling molecules containing the Src homology 2 (SH2) domain, such as phosphatidyl inositol (PI)-3 kinase, 6 phospholipase C␥1, 7,8 Grb2, and the Src kinase, 9 to c-Kit and initiates cytoplasmic signaling. In addition to KitL/c-Kit signaling, interleukin (IL)-3 is also involved in mast cell development. IL-3-deficient mice maintain a basal level of mast cells, whereas mast cells fail to expand in response to infection by the nematode Stronglyoides venezuelensis. 10 Double-mutant Kit W /Kit W-v , IL-3 Ϫ/Ϫ mice display a more severe reduction in mast cell and basophil expansion elicited by the nematode infection than do single-mutant mice. 10 The result suggests that IL-3 is not essential for the generation of mast cells in a resting state but that it is required for the increase in mast cells in the immune response elicited by parasites. On the other hand, KitL-mediated signals are required for the development of the basal level of mast cells.Gab2 is a member of the Gab/DOS family of adapter molecules, which contain a pleckstrin homology (PH) domain and potential binding sites for the SH2 and SH3 domains. [11][12][13][14] Gab2 is tyrosine phosphorylated on stimulation by growth factors, cytokines, and Tand B-cell antigen receptors, including KitL and IL-3, and phosphorylated Gab2 binds SHP-2 and p85 PI-3 kinase. 11,15,16 Overexpression of Gab2 enhances the activation of cytokine-dependent ERK mitogen-activated protei...

Symbiotic digestion of lignocellulose in wood-feeding higher termites (family Termitidae) is a two-step process that involves endogenous host cellulases secreted in the midgut and a dense bacterial community in the hindgut compartment. The genomes of the bacterial gut microbiota encode diverse cellulolytic and hemicellulolytic enzymes, but the contributions of host and bacterial symbionts to lignocellulose degradation remain ambiguous. Our previous studies of Nasutitermes spp. documented that the wood fibers in the hindgut paunch are consistently colonized not only by uncultured members of Fibrobacteres, which have been implicated in cellulose degradation, but also by unique lineages of Spirochaetes. Here, we demonstrate that the degradation of xylan, the major component of hemicellulose, is restricted to the hindgut compartment, where it is preferentially hydrolyzed over cellulose. Metatranscriptomic analysis documented that the majority of glycoside hydrolase (GH) transcripts expressed by the fiber-associated bacterial community belong to family GH11, which consists exclusively of xylanases. The substrate specificity was further confirmed by heterologous expression of the gene encoding the predominant homolog. Although the most abundant transcripts of GH11 in Nasutitermes takasagoensis were phylogenetically placed among their homologs of Firmicutes, immunofluorescence microscopy, compositional binning of metagenomics contigs, and the genomic context of the homologs indicated that they are encoded by Spirochaetes and were most likely obtained by horizontal gene transfer among the intestinal microbiota. The major role of spirochetes in xylan degradation is unprecedented and assigns the fiber-associated Treponema clades in the hindgut of wood-feeding higher termites a prominent part in the breakdown of hemicelluloses.

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