The Role of Intestinal Microbiota in Acute Graft-versus-Host Disease

Figure 1

Schematic of the role of microbiota in graft-versus-host disease in the gut. Under normal conditions, the intestinal epithelial surface maintains an intact barrier function that prevents bacterial invasion into deeper host tissues. Paneth cells secrete several microbicidal proteins, including α-defensins, which selectively kill pathogenic bacteria. Bacteroides fragilis-derived TLR capsular polysaccharide A can promote the induction of Treg cells. Segmented filamentous bacteria (SFB) induce production of serum amyloid A (SAA) in the gut, and SAA acts on dendritic cells (DCs) to promote Th17 cell differentiation. After total body irradiation (TBI) and chemotherapy as part of the conditioning regimen, the integrity of the intestinal surface is decreased. Intestinal bacteria and their components (pathogen-associated molecular patterns, PAMPs) translocate to the lamina propria and are recognized by Toll-like receptors (TLRs) in host antigen-presenting cells (APCs). Activated APCs secrete proinflammatory cytokines and prime donor T cells, which aggravate acute GVHD.