This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hajishengallis, G.
Right arrow Articles by Connell, T. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hajishengallis, G.
Right arrow Articles by Connell, T. D.

 Previous Article  |  Next Article 

Infection and Immunity, November 2004, p. 6351-6358, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6351-6358.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

The Type II Heat-Labile Enterotoxins LT-IIa and LT-IIb and Their Respective B Pentamers Differentially Induce and Regulate Cytokine Production in Human Monocytic Cells

George Hajishengallis,1* Hesham Nawar,2 Richard I. Tapping,3 Michael W. Russell,2 and Terry D. Connell2

Department of Microbiology, Immunology, and Parasitology, Center of Excellence in Oral and Craniofacial Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana,1 Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, University of Buffalo, New York,2 Department of Microbiology, University of Illinois, Urbana, Illinois3

Received 17 May 2004/ Returned for modification 3 August 2004/ Accepted 11 August 2004

The type II heat-labile enterotoxins, LT-IIa and LT-IIb, exhibit potent adjuvant properties. However, little is known about their immunomodulatory activities upon interaction with innate immune cells, unlike the widely studied type I enterotoxins that include cholera toxin (CT). We therefore investigated interactions of LT-IIa and LT-IIb with human monocytic THP-1 cells. We found that LT-II enterotoxins were inactive in stimulating cytokine release, whereas CT induced low levels of interleukin-1ß (IL-1ß) and IL-8. However, all three enterotoxins potently regulated cytokine induction in cells activated by bacterial lipopolysaccharide or fimbriae. Induction of proinflammatory (tumor necrosis factor {alpha} [TNF-{alpha}]) or chemotactic (IL-8) cytokines was downregulated, whereas induction of cytokines with anti-inflammatory (IL-10) or mucosal adjuvant properties (IL-1ß) was upregulated by the enterotoxins. These effects appeared to depend on their A subunits, because isolated B-pentameric subunits lacked regulatory activity. Enterotoxin-mediated inhibition of proinflammatory cytokine induction in activated cells was partially attributable to synergism for endogenous production of IL-10 and to an IL-10-independent inhibition of nuclear factor {kappa}B (NF-{kappa}B) activation. In sharp contrast to the holotoxins, the B pentamers (LT-IIaB and, to a greater extent, LT-IIbB) stimulated cytokine production, suggesting a link between the absence of the A subunit and increased proinflammatory properties. In this regard, the ability of LT-IIbB to activate NF-{kappa}B and induce TNF-{alpha} and IL-8 was antagonized by the LT-IIb holotoxin. These findings support distinct immunomodulatory roles for the LT-II holotoxins and their respective B pentamers. Moreover, the anti-inflammatory properties of the holotoxins may serve to suppress innate immunity and promote the survival of the pathogen.

* Corresponding author. Mailing address: LSU Health Sciences Center, Department of Microbiology, Immunology, and Parasitology, Center of Excellence in Oral and Craniofacial Biology, 1100 Florida Ave., Box 130, New Orleans, LA 70119. Phone: (504) 619-8709. Fax: (504) 670-2736. E-mail: ghajis{at}lsuhsc.edu.

Editor: J. D. Clements

Infection and Immunity, November 2004, p. 6351-6358, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6351-6358.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Liang, S., Hosur, K. B., Lu, S., Nawar, H. F., Weber, B. R., Tapping, R. I., Connell, T. D., Hajishengallis, G. (2009). Mapping of a Microbial Protein Domain Involved in Binding and Activation of the TLR2/TLR1 Heterodimer. J. Immunol. 182: 2978-2985 [Abstract] [Full Text]  
  • Liang, S., Wang, M., Triantafilou, K., Triantafilou, M., Nawar, H. F., Russell, M. W., Connell, T. D., Hajishengallis, G. (2007). The A Subunit of Type IIb Enterotoxin (LT-IIb) Suppresses the Proinflammatory Potential of the B Subunit and Its Ability to Recruit and Interact with TLR2. J. Immunol. 178: 4811-4819 [Abstract] [Full Text]  
  • Liang, S., Wang, M., Tapping, R. I., Stepensky, V., Nawar, H. F., Triantafilou, M., Triantafilou, K., Connell, T. D., Hajishengallis, G. (2007). Ganglioside GD1a Is an Essential Coreceptor for Toll-like Receptor 2 Signaling in Response to the B subunit of Type IIb Enterotoxin. J. Biol. Chem. 282: 7532-7542 [Abstract] [Full Text]  
  • Arce, S., Nawar, H. F., Muehlinghaus, G., Russell, M. W., Connell, T. D. (2007). In Vitro Induction of Immunoglobulin A (IgA)- and IgM-Secreting Plasma Blasts by Cholera Toxin Depends on T-Cell Help and Is Mediated by CD154 Up-Regulation and Inhibition of Gamma Interferon Synthesis. Infect. Immun. 75: 1413-1423 [Abstract] [Full Text]  
  • Nawar, H. F., Arce, S., Russell, M. W., Connell, T. D. (2007). Mutants of Type II Heat-Labile Enterotoxin LT-IIa with Altered Ganglioside-Binding Activities and Diminished Toxicity Are Potent Mucosal Adjuvants. Infect. Immun. 75: 621-633 [Abstract] [Full Text]  
  • Harokopakis, E., Albzreh, M. H., Martin, M. H., Hajishengallis, G. (2006). TLR2 Transmodulates Monocyte Adhesion and Transmigration via Rac1- and PI3K-Mediated Inside-Out Signaling in Response to Porphyromonas gingivalis Fimbriae.. J. Immunol. 176: 7645-7656 [Abstract] [Full Text]  
  • Allen, K. P., Randolph, M. M., Fleckenstein, J. M. (2006). Importance of Heat-Labile Enterotoxin in Colonization of the Adult Mouse Small Intestine by Human Enterotoxigenic Escherichia coli Strains. Infect. Immun. 74: 869-875 [Abstract] [Full Text]  
  • Hajishengallis, G., Arce, S., Gockel, C.M., Connell, T.D., Russell, M.W. (2005). Immunomodulation with Enterotoxins for the Generation of Secretory Immunity or Tolerance: Applications for Oral Infections. JDR 84: 1104-1116 [Abstract] [Full Text]  
  • Hajishengallis, G., Ratti, P., Harokopakis, E. (2005). Peptide Mapping of Bacterial Fimbrial Epitopes Interacting with Pattern Recognition Receptors. J. Biol. Chem. 280: 38902-38913 [Abstract] [Full Text]  
  • Arce, S., Nawar, H. F., Russell, M. W., Connell, T. D. (2005). Differential Binding of Escherichia coli Enterotoxins LT-IIa and LT-IIb and of Cholera Toxin Elicits Differences in Apoptosis, Proliferation, and Activation of Lymphoid Cells. Infect. Immun. 73: 2718-2727 [Abstract] [Full Text]  
  • Hajishengallis, G., Tapping, R. I., Martin, M. H., Nawar, H., Lyle, E. A., Russell, M. W., Connell, T. D. (2005). Toll-Like Receptor 2 Mediates Cellular Activation by the B Subunits of Type II Heat-Labile Enterotoxins. Infect. Immun. 73: 1343-1349 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»