Recent progress on pathophysiology, inflammation and defense mechanism of mast cells against invading microbes: inhibitory effect of IL-37.

Mast cells (MCs) have historically been considered masters of allergy, but there is substantial evidence supporting their contribution to tissue microorganism clearance. Their activation through the cross-linking of bound IgE provokes mast cell degranulation and activates tyrosine kinase (Syk and Lyn), leading to cytokine/chemokine generation and release. Current consensus holds that mast cells participate in the body's defense against numerous pathogens, including bacteria, fungi, viruses and parasites, but also contribute to the inflammatory response induced by these biological agents. In the light of the latest findings, we describe the cross-talk between mast cells and pathogenic microorganisms. This review summarizes our current understanding of the host immune response, with emphasis on the roles of MCs and the cytokine/chemokine network in provoking inflammation and generating protective immunity. This review addresses the ability of microorganisms to activate MCs provoking inflammation. We describe some MC-specific biological activities related to infections and discuss the evidence of MC mechanisms involved in the microbial activation which cause cytokine/chemokine generation-mediated inflammation, and provide a description of novel functions of mast cells during microbial infection. Interleukin (IL)-37 binds the α chain of the IL-18 receptor and suppresses MyD88-mediated inflammatory responses. IL-37 plays a pathological role in certain infections by inhibiting the production of pro-inflammatory cytokines, such as IL-1 and TNF. Here we report the interrelationship between IL-37, inflammatory cytokines and mast cells. Our report offers opportunities for the design of new therapeutic interventions in inflamed tissue induced by microorganism infections, acting on manipulation of mast cells and/or inflammatory cytokine blockage.