Previous Article | Next Article 
Infection and Immunity, March 2002, p. 1150-1158, Vol. 70, No. 3
0019-9567/02/$04.00+0 DOI: 10.1128/IAI.70.3.1150-1158.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Shigella flexneri Interactions with the Basolateral Membrane Domain of Polarized Model Intestinal Epithelium: Role of Lipopolysaccharide in Cell Invasion and in Activation of the Mitogen-Activated Protein Kinase ERK
Henrik Köhler, Sonia P. Rodrigues, and Beth A. McCormick*
Mucosal Immunology Laboratory, Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129
Received 11 September 2001/
Returned for modification 22 October 2001/
Accepted 12 December 2001
An early step governing Shigella flexneri pathogenesis is the invasion of the colonic epithelium from the basolateral surface followed by disruption of the colonic epithelial barrier. Despite recent insight into S. flexneri-host interactions, much remains to be determined regarding the nature of the initial contact between S. flexneri and the host epithelial basolateral membrane domain. Since the lipopolysaccharide (LPS) is located at the outermost part of the bacterial membrane, we considered that this component might be used by S. flexneri to attach to the basolateral surface of the intestinal epithelium and promote a proinflammatory response. Therefore, polarized human T84 intestinal epithelial cells were infected from the basolateral surface with either wild-type S. flexneri or one of its isogenic LPS-defective strains with mutations in either rfc, rfaL, or galU. We found that both adherence to and internalization into the basolateral surface of a polarized intestinal epithelium with S. flexneri were highly dependent on the length of the LPS (i.e., rfc > rfaL > galU). Furthermore, the addition of the anti-inflammatory LPS (RsDPLA) considerably decreased the invasion profile of wild-type S. flexneri by nearly 50%. Since LPS is associated with host inflammation, we further examined whether this molecule was involved in Shigella-induced inflammatory events. We found that S. flexneri LPS plays an important role in mediating epithelial-derived signaling, which leads to directed migration of polymorphonuclear leukocytes across model intestinal epithelium. This signaling most likely involves the activation of the mitogen-activated protein kinase extracellular regulated kinase. Thus, our findings have important implications on the understanding of the mechanisms by which S. flexneri can elicit mucosal inflammation.
* Corresponding author. Mailing address: Department of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, 114 16th St. (114-3503), Charlestown, MA 02129. Phone: (617) 726-4168. Fax: (617) 726-4172. E-mail:
mccormic{at}helix.mgh.harvard.edu.
Infection and Immunity, March 2002, p. 1150-1158, Vol. 70, No. 3
0019-9567/02/$04.00+0 DOI: 10.1128/IAI.70.3.1150-1158.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Carter, J. A., Jimenez, J. C., Zaldivar, M., Alvarez, S. A., Marolda, C. L., Valvano, M. A., Contreras, I.
(2009). The cellular level of O-antigen polymerase Wzy determines chain length regulation by WzzB and WzzpHS-2 in Shigella flexneri 2a. Microbiology
155: 3260-3269
[Abstract]
[Full Text]
-
Whitlock, G. C., Valbuena, G. A., Popov, V. L., Judy, B. M., Estes, D. M., Torres, A. G.
(2009). Burkholderia mallei cellular interactions in a respiratory cell model. J Med Microbiol
58: 554-562
[Abstract]
[Full Text]
-
Mumy, K. L., Bien, J. D., Pazos, M. A., Gronert, K., Hurley, B. P., McCormick, B. A.
(2008). Distinct Isoforms of Phospholipase A2 Mediate the Ability of Salmonella enterica Serotype Typhimurium and Shigella flexneri To Induce the Transepithelial Migration of Neutrophils. Infect. Immun.
76: 3614-3627
[Abstract]
[Full Text]
-
Molinaro, A., Silipo, A., Castro, C. D., Sturiale, L., Nigro, G., Garozzo, D., Bernardini, M. L., Lanzetta, R., Parrilli, M.
(2008). Full structural characterization of Shigella flexneri M90T serotype 5 wild-type R-LPS and its {Delta}galU mutant: glycine residue location in the inner core of the lipopolysaccharide. Glycobiology
18: 260-269
[Abstract]
[Full Text]
-
Mumy, K. L., Chen, X., Kelly, C. P., McCormick, B. A.
(2008). Saccharomyces boulardii interferes with Shigella pathogenesis by postinvasion signaling events. Am. J. Physiol. Gastrointest. Liver Physiol.
294: G599-G609
[Abstract]
[Full Text]
-
Zurawski, D. V., Mumy, K. L., Badea, L., Prentice, J. A., Hartland, E. L., McCormick, B. A., Maurelli, A. T.
(2008). The NleE/OspZ Family of Effector Proteins Is Required for Polymorphonuclear Transepithelial Migration, a Characteristic Shared by Enteropathogenic Escherichia coli and Shigella flexneri Infections. Infect. Immun.
76: 369-379
[Abstract]
[Full Text]
-
Carter, J. A., Blondel, C. J., Zaldivar, M., Alvarez, S. A., Marolda, C. L., Valvano, M. A., Contreras, I.
(2007). O-antigen modal chain length in Shigella flexneri 2a is growth-regulated through RfaH-mediated transcriptional control of the wzy gene. Microbiology
153: 3499-3507
[Abstract]
[Full Text]
-
Li, H., Xu, H., Zhou, Y., Zhang, J., Long, C., Li, S., Chen, S., Zhou, J.-M., Shao, F.
(2007). The Phosphothreonine Lyase Activity of a Bacterial Type III Effector Family. Science
315: 1000-1003
[Abstract]
[Full Text]
-
Zurawski, D. V., Mitsuhata, C., Mumy, K. L., McCormick, B. A., Maurelli, A. T.
(2006). OspF and OspC1 Are Shigella flexneri Type III Secretion System Effectors That Are Required for Postinvasion Aspects of Virulence.. Infect. Immun.
74: 5964-5976
[Abstract]
[Full Text]
-
Chanchevalap, S., Nandan, M. O., McConnell, B. B., Charrier, L., Merlin, D., Katz, J. P., Yang, V. W.
(2006). Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells. Nucleic Acids Res
34: 1216-1223
[Abstract]
[Full Text]
-
Hurley, B. P., Siccardi, D., Mrsny, R. J., McCormick, B. A.
(2004). Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3. J. Immunol.
173: 5712-5720
[Abstract]
[Full Text]
-
Priebe, G. P., Dean, C. R., Zaidi, T., Meluleni, G. J., Coleman, F. T., Coutinho, Y. S., Noto, M. J., Urban, T. A., Pier, G. B., Goldberg, J. B.
(2004). The galU Gene of Pseudomonas aeruginosa Is Required for Corneal Infection and Efficient Systemic Spread following Pneumonia but Not for Infection Confined to the Lung. Infect. Immun.
72: 4224-4232
[Abstract]
[Full Text]
-
Edwards-Jones, B., Langford, P. R., Kroll, J. S., Yu, J.
(2004). The role of the Shigella flexneri yihE gene in LPS synthesis and virulence. Microbiology
150: 1079-1084
[Abstract]
[Full Text]
-
Lawrence, M. L., Banes, M. M., Azadi, P., Reeks, B. Y.
(2003). The Edwardsiella ictaluri O polysaccharide biosynthesis gene cluster and the role of O polysaccharide in resistance to normal catfish serum and catfish neutrophils. Microbiology
149: 1409-1421
[Abstract]
[Full Text]
-
Berkes, J, Viswanathan, V K, Savkovic, S D, Hecht, G
(2003). Intestinal epithelial responses to enteric pathogens: effects on the tight junction barrier, ion transport, and inflammation. Gut
52: 439-451
[Abstract]
[Full Text]
-
Keely, S. J., Barrett, K. E.
(2003). p38 mitogen-activated protein kinase inhibits calcium-dependent chloride secretion in T84 colonic epithelial cells. Am. J. Physiol. Cell Physiol.
284: C339-C348
[Abstract]
[Full Text]