Bacteria in the Intestine, Helpful Residents or Enemies from Within?Geraldine O. Canny and Beth A. McCormick




Schematic diagrams of small intestine mucosa in normal and infected intestines. (A) Normal intestinal mucosa, including the epithelial layer with the associated brush border, tight junctions, mucosa, and the microbiota. There are small cells at the intestinal crypts (Paneth cells) that secrete large amounts of antimicrobial peptides (defensins). A large M cell with a closely associated phagocyte is also shown. Even during the resting state some of these entrocytes express the cytoplasmic microbial pattern recognition receptors (PRR) (i.e., NOD2). (B) Infected intestinal mucosa. A typical diseased intestinal epithelium during bacterial insult is shown. On the left side (cells labeled A to C) an M cell (cell A) takes up S. enterica serovar Typhimurium after the bacterium injects its effectors through the type III secretion system (TTSS), leading to the formation of a Salmonella-containing vacuole (SCV) and eventual host cell death. Cell death liberates the bacteria, which can invade the incoming phagocytes. For a neighboring cell (cell C) the key events of the host cell response are shown, which includes LPS activation of a surface pattern recognition receptor (TLR4), leading to MyD88-dependent activation of NF-B and basolateral release of IL-8 (CXCL8). At the same time the intracellular pattern recognition receptor, NOD2, recognizes a bacterial peptidoglycan (PG) derivative and triggers a pathway that culminates in NF-B activation. The epithelial cells also secrete the PMN chemoattractant hepoxilin A3 (HXA3) at the apical surface, resulting in an influx of neutrophils into the mucosa and lumen from the underlying vascular bed. On the right side (cells D and E) EPEC and V. cholerae infection is shown. Cell D loosens the brush border and tight junction due to the bacterial effectors secreted by the type III secretion system. In the case of cell E the result is almost same, but the outcome is due to a toxin secreted by V. cholerae. FA, fatty acid.

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