Fig. 1

Major components of the intestinal barrier comprising the following four layers. (1) The mucus layer protects against microbial invasion by secreted substances such as mucin from goblet cells, IgA antibodies from the intestinal mucosal layer, and antimicrobial peptides from Paneth cells. This layer is divided into an outer mucus layer that supports the growth of commensal bacteria and an inner mucus layer that protects against bacterial invasion. (2) The epithelial layer contains enterocytes, goblet cells, Paneth cells, and M cells. Intraepithelial lymphocytes (IELs) are abundant. Tight junctions prevent physical bacterial invasion, while M cells sample luminal microorganisms for mucosal immune surveillance. (3) The mucosal intrinsic layer possesses an active immune barrier that contains T cells, B cells, macrophage, dendritic cells (DCs), and innate immune-like cells such as MAIT cells. DCs extend their projections to directly inspect and transport microbes to mesenteric lymph nodes (MLNs). (4) The gut-vascular barrier (GVB), consisting of a structured endothelium, is an independent barrier that regulates the translocation of luminal bacteria and their ligands as well as innocuous food antigens. MLNs act as primary firewall that prevents microbes from entering the systemic circulation. When bacteria invade the GVB, they reach the liver via the portal vein. The liver, which is enriched with immune cells such as Kupffer cells and MAIT cells, serves as second firewall. IgA, immunoglobulin A; M cells, microfold cells; MAIT cells, mucosal-associated invariant T cells; TJ, tight junction