Figure 1. Potential mechanisms of IgE-independent mast cell activation and tissue-derived cytokine induction during intestinal helminth infection. Activation (Left panel): Helinth derived antigens, immunomodulators and proteases along with concurrent stimulation by commensal derived molecules and/or dangers signals can be recognized by mast cells through a variety or receptors including Toll-like receptors (TLRs), NOD-like receptors (NLRs) and “alarmin” receptors (e.g., IL-33R). Response (Right panel): Following stimulation mast cells respond via degranulation and/or the synthesis of cytokines, possibly include IL-25, IL-33 and TSLP. Moreover, mast cell inflammatory mediators have the ability to cross talk with other cells, such as epithelial cells, to induce the production of tissue-derived cytokines that are ultimately required for the optimal orchestration, amplification and priming of Th2 responses toward gastrointestinal helminths.