The capsular polysaccharide of Vibrio cholerae O139 Bengal: Induction and modulation of host-cell mediated immune responses
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AbstractCholera is a severe and sometimes lethal secretory diarrheal disease caused by Vibrio cholerae. V. cholerae 0139 produce a diarrheal disease indistinguishable from cholera due to V. cholerae 01, however, the intestinal pathologies are different. V. cholerae 0139 infection is associated with intestinal inflammation and tissue destruction, which is not seen with V. cholerae 01. In addition, septicemia and bacteremia can occur with V. cholerae 0139 infection. V. cholerae 0139 isolates possess the same virulence factors as V. cholerae 01; however, they additionally express a capsule (CPS) and a distinct lipopolysaccharide (LPS). We have found that V. cholerae 0139 CPS (Vc CPS) induced the secretion of IL-8, G-CSF, IL-1beta, and to a lesser degree TNF-alpha and IL-6. Encapsulation of V. cholerae 0139 hindered phagocytosis and significantly decreased TNF-alpha secretion from human PBMCs. Purified VcCPS suppressed TNF-alpha secretion from PBMCs in response to unencapsulated V. cholerae 0139 bacterial cells as well as E. coli LPS (EcLPS). In contrast, VcCPS up-regulated IL-1beta secretion in response to EcLPS and VcLPS, but had no effect on IL-8 secretion. Using T84 intestinal monolayers, neither purified CPS nor LPS could induce significant IL-8 secretion from T84 intestinal monolayers. Surprisingly, no significant differences in IL-8 secretion in response to either acapsular or encapsulated V. cholerae 0139 were detected, and both strains were able to induce PMN transmigration across T84 monolayers. Using electron microscopy, V. cholerae 0139 infection was found to produce vacuolation of T84 monolayers, a phenomenon not observed with acapsular V. cholerae 0139. In the in vivo rabbit reversible intestinal tie adult rabbit diarrhea (RITARD) model, we did not find evidence of V. cholerae 0139 mucosal invasion, tissue damage, nor any significant inflammation as previously reported in ileal loop models. These results suggest that the capsule of V. cholerae 0139 may serve to down-regulate the acute inflammatory response in both the bloodstream as well as the intestines. Such a property increases the bacteria's ability to survive in the host environment and consequently is a significant component of pathogenesis. Understanding the role of the capsule in V. cholerae 0139 infection may potentially aid in vaccine development and the prevention of disease.
DescriptionUniversity of Maryland, Baltimore. Medical Pathology. Ph.D. 2001
Health Sciences, Immunology
Vibrio cholerae 0139--immunology
Vibrio cholerae 0139--pathogenicity