On June 1–2, 2009, NIAID/DAIT sponsored a workshop entitled Mast Cells in Innate and Adaptive Immunity. Workshop participants included international experts in mast cell biology who, in six workshop sessions, addressed key issues on signaling and activation, mediators of innate immune responses, comparisons of animal model and human studies, host defense CHIR-99021 against pathogens, adjuvant properties of mast cell activators and products, and recommendations for future research. Although mast cells were first described well over a century ago (as reviewed in 4), the main functions of mast cells other than as effectors in allergic diseases still remain unclear. Dean Metcalfe (Bethesda, MD) noted that

a large body of knowledge generated about mast cells in the context of allergic diseases has, however, also contributed to an understanding of the roles of mast cells in inflammation and host defense. The overall importance of mast cells as sentinels is emphasized by the observation that the size of the mast cell pool in mammals is roughly equivalent to the number of cells in the spleen. As mediators of innate host defense, mast cells express most TLR as well as Nod-like

receptors (NLR), and they not only recognize bacteria, but phagocytose and kill them directly. Dr. Metcalfe also observed that relatively Alvelestat nmr little is known about their role in viral infections, although in the context of HIV infection, mast cells appear to represent a significant viral reservoir 5. Nintedanib (BIBF 1120) Thus, mast cell activation in AIDS patients may result in the same problems previously observed after the activation of HIV-infected T cells, i.e. the release of virus. Dr. Metcalfe listed the major challenges hampering the field such as the difficulty in culturing human mast cells, the need for more robust animal models and a better understanding of their relevance to human diseases, and the identification of pharmaceutical agents that target mast cells. The limited understanding

of mast cell function in the defense against infectious agents extends to molecular events. Juan Rivera (Bethesda, MD) observed that signals resulting from cross-linking of high-affinity IgE receptors (FcεRI) on mast cells have been studied extensively in the context of allergy, but little is known about the consequences of engaging other immune and nonimmune mast cell receptors. Mast cell responses to stimulation are very heterogeneous, depending on the types of receptors that are triggered and the sets of downstream kinases that are activated. Receptor engagement on mast cells can trigger either positive (stimulatory e.g. FcεRI) or negative (inhibitory) pathways. Dr. Rivera’s laboratory has uncovered evidence that some of these signals trigger irreversible epigenetic changes in long-lived mast cells rendering them permanently hyper-responsive 6, 7.