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Role of lipopolysaccharide in signaling to subepithelial polymorphonuclear leukocytes
1Unité de Pathogénie Microbienne Moléculaire, U389, Institut Nationale de la Santé et de la Recherche Médicale, Institut Pasteur, Paris, France.
Abstract:
Polymorphonuclear leukocyte (PMN) infiltration and migration across colonic intestinal epithelia is a hallmark of inflammation in Shigella flexneri-mediated dysentery. To identify bacterial signals associated with this process, potential stimulatory factors mediating initial PMN association with the epithelium and subsequent transepithelial migration were examined in an in vitro model system. Quantitative analyses revealed that purified S. flexneri lipopolysaccharide (LPS) deposited at the apical surface of polarized intestinal epithelial cells transcytosed to the basolateral pole, a process dependent on the stage of epithelial cell differentiation. Transcytosed LPS in the presence of normal human serum (NHS), a source of LPS binding protein and soluble CD14, mediated both interleukin-8 secretion at the basolateral pole and enhanced PMN adherence. In addition, LPS stimulated a significant degree of directed transepithelial migration of PMNs, an event that was further enhanced in the presence of NHS. These results implicate LPS in signaling subepithelial PMN emigration and enhancing PMN-epithelium interactions prior to and during subsequent Shigella-induced transepithelial migration.
Insights
Shigella flexneri lipopolysaccharide (LPS) signals polymorphonuclear leukocyte (PMN) migration during dysentery. Transcytosed LPS enhances PMN adherence and transepithelial migration, crucial for inflammatory responses.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Polymorphonuclear leukocyte (PMN) infiltration is key in Shigella flexneri dysentery.
- Bacterial signals driving PMN transepithelial migration are not fully understood.
Purpose of the Study:
- Identify bacterial factors mediating PMN association and migration across intestinal epithelia.
- Investigate the role of Shigella flexneri lipopolysaccharide (LPS) in PMN-epithelial interactions.
Main Methods:
- Utilized an in vitro model of polarized intestinal epithelial cells.
- Examined the transcytosis of purified S. flexneri LPS.
- Assessed PMN adherence and transepithelial migration in response to LPS, with and without normal human serum (NHS).
Main Results:
- S. flexneri LPS transcytosed from apical to basolateral epithelial surfaces, dependent on cell differentiation stage.
- Transcytosed LPS, with NHS, induced interleukin-8 secretion and enhanced PMN adherence.
- LPS significantly promoted directed PMN transepithelial migration, further enhanced by NHS.
Conclusions:
- S. flexneri LPS is implicated in signaling subepithelial PMN emigration.
- LPS enhances PMN-epithelium interactions during Shigella-induced inflammation.