A small inoculum of Shigella (10 to 200 organisms) is sufficient to cause shigellosis. Shigella is commonly spread by the fecal-oral route in regions of poor sanitation (foodborne or waterborne transmission). Shigella first invades the epithelial cells of the large intestine by using M cells as entry ports for transcytosis. Shigella then invades macrophages and induces cellular apoptosis, which results in inflammation, generation of proinflammatory cytokines, and recruitment of polymorphonuclear neutrophils (PMNs). Following transcytosis and macrophage apoptosis, Shigella avoids extracellular exposure and spreads intercellularly using actin polymerization processes (rocket propulsion). As PMN invade the site of active inflammation, the integrity of the intestinal epithelial barrier is lost, and adsorption of fluids and nutrients is impaired, resulting in clinical manifestations of shigellosis (e.g. diarrhea). On gross pathology, hyperemia with development of ulcers and edema are typical findings. On microscopic pathology, infiltration of PMN and inflammatory pseudomembranes are characteristic features.

• A small inoculum of Shigella (10 to 200 organisms) is sufficient to cause shigellosis.^[1]
• Shigella is commonly spread by the fecal-oral route in regions with poor sanitation.^[1][2]
• Exposure to contaminated food (e.g. vegetables or meat) or water (drinking or swimming in untreated water) is associated with shigellosis. Contaminated food and water may have a normal appearance and smell.
• Epidemics may be foodborne or waterborne.^[1]
• Shigella can also be transmitted by flies and sexual contact.^[2]

The small inoculum may be attributed to the following features of the organism:

• Shigella contains acid resistance systems that enable the organism to survive the acidic environment in the stomach.^[3]
• Shigella can downregulate the expression of antibacterial proteins released by the host (human) intestinal mucosa.^[4]

Shigella migrates to the large intestine, where it causes infection via invasion of the epithelial barrier of the large intestine. Initially, Shigella uses M cells from the basolateral side of the intestinal epithelium as entry port.^[5] M cells are specialized cells that sample the gut lumen for pathogenic antigens and delivers these antigens to mucosal lymphoid tissue to activate an adequate immune response.^[6] Shigella is transcytosed across the epithelial layer of the intestinal M cells.

• Following transcytosis, Shigella enters macrophages and induces cellular apoptosis.^[7]
• Macrophage apoptosis results in the release of proinflammatory cytokines (IL-1-beta and IL-18), which signal intestinal inflammation and consequent activation of the innate immune system.^[8][9]

• Following apoptosis and inflammation, Shigella is released from the macrophages.^[10]
• Invasion of the intestinal epithelium continues from the basolateral side, and the bacteria further spreads to adjacent epithelial cells and avoids extracellular exposure by using intercellular actin polymerization processes (rocket propulsion).^[11]

• As Shigella infiltrates the epithelial cells, activation of nuclear factor kappa-B (NF-KB) by Shigella generates IL-8, which in turn mediates the recruitment of polymorphonuclear neutrophils (PMN) to the site of inflammation.^[12]
• PMN destroy the integrity of the intestinal epithelial barrier and allow more Shigella organisms to directly and more easily invade the intestinal epithelium. The loss of the intestinal epithelial cells results in impaired adsorption of other nutrients and fluids and leads to clinical manifestations of shigellosis (diarrhea).^[2]
• Shigella enterotoxin 1 (ShET1) and enterotoxin 2 (ShET2) are synthesized during the inflammatory process and are thought to account, at least in part, for fluid secretion that results in shigellosis-associated diarrhea.^[13]
• Other Shigella toxins, such as Shigella dysenteriae serotype 1 toxin, results in cytotoxicity and development of vascular lesions at the level of the colon, the kidneys, and the central nervous system. The cytotoxic activity of the toxin is thought to cause shigella-associated complications, such as hemolytic uremic syndrome (HUS).^[14]

Ultimately, more PMNs are recruited and Shigella organisms are killed.

On gross pathology, shigellosis is typically associated with acute-onset diffuse fibrinous exudative inflammation in the colon and/or the rectum. The following histopathological features may be observed:

• Ulcer formation and focal erosions
• Necrotizing inflammation
• Hyperemia
• Edema

On microscopic histopathological analysis, the following findings may be observed from samples of the colon, rectum, and occasionally the distal ileum:

• PMN infiltration
• Formation of patchy inflammatory pseudomembrane

The following video demonstrates the microscopic pathological features of shigellosis: {{#ev:youtube|1D1m4rybDrc}}

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