Pathogenesis of infectious diarrhea: GUT PHYSIOLOGY Part 8

GUT PHYSIOLOGY Part 8Non-histotoxic Salmonella species: Non-histotoxic Salmonella species are an example of a pathogen that causes shortening of whole villi. Here, the picture, as observed in the rabbit ileal loop model, is totally different from that described for histotoxic Salmonella species. Bacteria enter via brush borders, and bacteria-laden cells are shed. There is no evidence of a rapid initial cleavage of tight junctions. The time scale of events is quite different from that seen with histotoxic Salmonella species, with maximum cell shedding, leading to truncation of villi, occurring at 12 to 14 h after challenge. Behind the extrusion of bacteria-laden cells, the epithelium is resealed. By 18 h, truncated villi appear ‘normal’, as judged by scanning electron microscopy, and begin to undergo reconstruction. Clearly, it is possible that, in such a situation, loss of the tip regions of villi could lead to loss of absorptive potential and hence contribute to secretion by unmasking, if not stimulating ‘normal’ secretion. flovent inhaler

This extensive study of both histotoxic and nonhisto-toxic Salmonella species has also thrown light on other aspects of the pathogenicity of this highly complex pathogen. First, we found no evidence for the idea that the host-restriction exhibited by Salmonella serotypes dublin and choleraesuis for cattle and pigs is explicable solely in terms of major differences in their respective invasiveness for terminal ileum.

Second, we found no evidence that entry of Salmonella species into the gut was obligatorily via M cells. There is now a growing acceptance, based largely on studies in murine-ligated loops, that M cells are the main primary route of the entry of Salmonella species into the gut in vivo. It is perceived that M cells then die, creating a gap in the epithelium through which bacteria can penetrate and then infect adjacent enterocytes via basolateral membranes, resulting in exfoliation of enterocytes, denudation of follicle-associated epithelium and exposure of the basement membrane to luminal bacteria. It is interesting to note that the damage seen in murine-ligated loops 2 h after infection (with very large doses of mouse virulent S typhimurium strain SL 1344), bears some similarity to that caused by histotoxic S dublin strain 3246 in pigs, calves and rabbits. It is possible that the disruption of murine epithelia was toxin-mediated as distinct from being a secondary undefined consequence of M cell destruction. The ‘M cell scenario’ may hold for S typhimurium in mice but certainly not in calves, where both M cells and enterocytes were infected very early in infection. In calves, infection of M cells and enterocytes occurred independently, separated in time by only 10 min. In both calves and pigs, no preference was shown by Salmonella species for FAE over AE as judged by quantitative recoveries of organisms from samples taken from the same ligated intestinal loop. In the rabbit, Peyer’s patches are discreet islands, and in all our work were avoided in the selection of ileal segments for both in vivo and in vitro experiments; Salmonella species readily invade enterocytes directly. In pigs infected with Salmonella cholerae-suis, it was possible to demonstrate the concurrent entry of organisms into both M cells and enterocytes, separated from each other in the same section.

This entry was posted in Diarrhea and tagged Bibrio cholerae, Clostridium difficile, Diarrhea, Escherichia coli, Shigella dysenteri.