Innate immunity and its regulation by mast cells

Abstract

Mast cells (MCs), which are granulated tissue-resident cells of hematopoietic lineage, constitute a major sensory arm of the innate immune system. In this review we discuss the evidence supporting the dual role of MCs, both as sentinels for invading pathogens and as regulatory cells throughout the course of acute inflammation, from its initiation to resolution. This versatility is dependent on the ability of MCs to detect pathogens and danger signals and release a unique panel of mediators to promote pathogen-specific clearance mechanisms, such as through cellular recruitment or vascular permeability. It is increasingly understood that MCs also contribute to the regulated contraction of immune activation that occurs within tissues as inflammation resolves. This overarching regulatory control over innate immune processes has made MCs successful targets to purposefully enhance or, alternatively, suppress MC responses in multiple therapeutic contexts.

Figure 1. Pathogen recognition and innate immune regulation by MCs

(a) MCs respond to diverse subtypes of pathogens and pathogen-associated motifs due to their expression of PRRs and additional unique cellular receptors. This panel summarizes the receptors that are used by MCs, the cellular location of the receptor (cell surface, vs. endosomal, vs. cytosolic) and the class of pathogen or PAMP that the receptor recognizes. (b) Unique events are promoted by MCs in response to different pathogens and based on tissue-specific MC capabilities. The release of MC products can promote cellular recruitment, vascular leakage, and other physical processes that are central to combating pathogens, such as mucus production. Additionally, MCs play a regulatory role in the tissue remodeling and immune contraction processes that must occur subsequent to inflammation in order to restore homeostasis.