Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis.

Abstract

SummaryThe gram-negative pathogen Shigella flexneri causes bacillary dysentery, an invasive disease of the human colonic mucosa. A major characteristic of the infectious process is the occurrence of an acute inflammatory reaction of mucosal tissues which is generally considered as a consequence of primary invasion and destruction of colonic epithelial cells by the pathogen. Confirming in vitro demonstration that S. flexneri is unable to invade the apical pole of colonic cells and that polymorphonuclear (PMN) cells may assist them in reaching the basal side of epithelial cells where they can invade, we have provided here in vivo evidence that S.flexneri enters the epithelial barrier essentially through the dome of lymphoid follicles at the early stage of infection and that subsequent invasion and destruction of the epithelium is primarily due to immigration of leukocytes, particularly PMN that destroy cohesion of the epithelial barrier. These conclusions are based on experiments carried out in infected rabbit ligated intestinal loops, with some animals treated by an anti-CD18 monoclonal antibody that blocked immigration of leukocytes into infected tissues.

Delivery of Biologically Active Anti-Inflammatory Cytokines IL-10 and IL-1ra In Vivo by the Shigella Type III Secretion Apparatus

“…Bacterial invasion of epithelial cells leads to destruction of the intestinal epithelium and accumulation of monocytes and polymorphonuclear leukocytes (PMN) 3 at the site of infection (1). The marked inflammation induced at the early stages of infection has paradoxical effects because it leads to further bacterial invasion through rupture of the epithelial cell barrier until complete control of infection occurs (2,3). Infection with wild-type S. flexneri results in invasion plasmid Ag (Ipa)B-dependent activation of caspase-1 in macrophages and to massive release of mature IL-1␤, which plays an important role in the initiation of inflammation (4).…”

Shigella reroutes host cell central metabolism to obtain high-flux nutrient supply for vigorous intracellular growth

“…An outstanding example is Shigella flexneri, which rapidly grow from a small infectious dose of 10-100 bacteria (1) to intestinal loads causing life-threatening bloody diarrhea (bacillary dysentery) within a few hours (2,3). This vigorous Shigella growth occurs inside human colon epithelial cells and requires an integrated Shigella pathogenesis program, including a type three secretion system encoded on the Shigella virulence plasmid.…”

Pathogenesis of spondylarthropathies

“…In contrast, Shigetla infects mainly epithelial cells (although a special role for macrophages has also been demonstrated recently) (49), where it produces only an acute infection, similar to that of Listeria; long-term intracellular persistence seems unlikely and has not been demonstrated. Shigella is a crucial pathogen in terms of this entire discussion, because Shigella-induced ReA has the highest B27 association and the highest association with complete Reiter's syndrome and with a chronic course of ReA (36,50).…”