Intestinal antigen-presenting cells in mucosal immune homeostasis: Crosstalk between dendritic cells, macrophages and B-cells

Abstract

The intestinal immune system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease (IBD) involves a breakdown in tolerance towards the microbiota. Dendritic cells (DC), macrophages (MΦ) and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Intestinal DC are migratory cells, unique in their ability to generate primary T-cell responses in mesenteric lymph nodes or Peyer’s patches, whilst MΦ and B-cells contribute to polarization and differentiation of secondary T-cell responses in the gut lamina propria. The antigen-sampling function of gut DC and MΦ enables them to sample bacterial antigens from the gut lumen to determine types of T-cell responses generated. The primary function of intestinal B-cells involves their secretion of large amounts of immunoglobulin A, which in turn contributes to epithelial barrier function and limits immune responses towards to microbiota. Here, we review the role of all three types of APC in intestinal immunity, both in the steady state and in inflammation, and how these cells interact with one another, as well as with the intestinal microenvironment, to shape mucosal immune responses. We describe mechanisms of maintaining intestinal immune tolerance in the steady state but also inappropriate responses of APC to components of the gut microbiota that contribute to pathology in IBD.

Keywords: Antigen presenting cells, Dendritic cells, Macrophages, B cells, Inflammatory bowel disease

Core tip: The intestinal immune-system maintains a delicate balance between immunogenicity against invading pathogens and tolerance of the commensal microbiota. Inflammatory bowel disease involves a breakdown in tolerance towards the microbiota. Dendritic cells, macrophages and B-cells are known as professional antigen-presenting cells (APC) due to their specialization in presenting processed antigen to T-cells, and in turn shaping types of T-cell responses generated. Here, we present an updated knowledge toward the role of these APC in intestinal immunity, both in the steady state and in inflammation, and how they interact with one another and with the intestinal microenvironment to shape mucosal immune responses.