PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11251877

Immunomodulation using bacterial enterotoxins.

C P Simmons·M Ghaem-Magami·L Petrovska·L Lopes·B M Chain·N A Williams·G Dougan
View original source ↗Export metadata ↓

Abstract

Immunologic unresponsiveness (tolerance) is a key feature of the mucosal immune system, and deliberate vaccination by a mucosal route can effectively induce immune suppression. However, some bacterial-derived proteins, e.g. cholera toxin and the heat labile toxin of Escherichia coli, are immunogenic and immunomodulatory at mucosal surfaces and can effectively adjuvant immune responses to codelivered bystander antigens. This review summarizes some of the structural and biological characteristics of these toxins and provides examples of how these properties have been exploited for tolerance induction and mucosal vaccine development.

Explore related subjects

Adjuvants, ImmunologicAnimalsAntigen-Presenting CellsBacterial ToxinsCD8-Positive T-LymphocytesCholera ToxinEnterotoxinsEscherichia coli ProteinsHumansImmunity, MucosalMiceModels, MolecularPoly(ADP-ribose) PolymerasesProtein SubunitsStructure-Activity RelationshipT-LymphocytesVirus DiseasesJournal ArticleResearch Support, Non-U.S. Gov'tReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C P Simmons, M Ghaem-Magami, L Petrovska, L Lopes, B M Chain, N A Williams, G Dougan. 2001. Immunomodulation using bacterial enterotoxins.. https://doi.org/10.1046/j.1365-3083.2001.00884.x

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2004

Improved immunogenicity of a self tumor antigen by covalent linkage to CD40 ligand.

The interaction between the CD40 ligand (CD40L) and CD40 on antigen-presenting cells (APCs) is critical in promoting humoral and cellular immune responses. Agonistic anti-CD40 monoclonal antibody and soluble CD40L can act as powerful adjuvants to promote vaccination, but usually require repeated high-dose treatment. In this study, we demonstrate that the adjuvant effect of CD40L can be greatly improved by directly linking the antigen to CD40L. We constructed a fusion protein (Id-CD40L) consisting of the extracellular domain of CD40L and the idiotype (Id) protein, a weakly immunogenic tumor-specific antigen derived from the murine 38C13 B-cell lymphoma. The soluble Id-CD40L fusion protein retained CD40 binding activity and stimulated CD80 and CD86 upregulation and interleukin (IL)-12 production by macrophages. Immunization of mice with Id-CD40L without adjuvants resulted in high titers of anti-Id Abs dominated by the IgG1 isotype and protected the mice from subsequent lethal tumor challenge. In a dose-response study, we demonstrated that Id-CD40L elicited anti-Id antibody (Ab) responses in all immunized animals, even at a dose as low as 0.5 microg. Immunization with free Id and an IgG-CD40L fusion protein, which was identical in structure to Id-CD40L but lost the Id determinant, resulted in significant lower anti-Id responses, indicating that physical linkage between the tumor antigen and CD40L was required for the optimal immune response. These results demonstrate that fusing CD40L to a candidate antigen can greatly improve the adjuvant activity of CD40L. This approach may be useful in developing vaccines for a variety of malignant and infectious diseases.

Adjuvants, Immunologic↗
PubMed2004

Structural studies of oligonucleotides containing G-quadruplex motifs using AFM.

G-quadruplex DNAs are cyclic arrays of four guanine bases binding by Hoogsteen hydrogen bonds, found in the telomeric regions of chromosomes and in transcriptional regulatory regions of several important oncogenes. Here, we used high resolution atomic force microscopy (AFM) to observe a specific guanine (G) tetrad mediated complex formation of oligonucleotides containing a G-quadruplex motifs (G-ODN) combined with a palindromic sequence under physiological extracellular conditions. These oligonucleotides have been investigated in correlation to their immunostimulatory effects. We observed structural dependence on ion concentration and G-ODN concentration, where high concentration self-assembled DNA networks were formed.

Adjuvants, Immunologic↗
PubMed2004

A method for peripheral chromatolysis in neurons of trigeminal and dorsal root ganglia, produced in rats by lithium.

In classical chromatolysis, Nissl bodies are initially lost centrally with subsequent progression to the periphery of the neuron. Peripheral chromatolysis has the opposite pattern; it is less common and more difficult to produce. We describe a new method for producing peripheral chromatolysis in neurons of trigeminal ganglia and dorsal root ganglia that requires only injection of large doses of lithium chloride (LiCl) for two, three or four consecutive daily doses. This method may be useful for elucidating the intraneuronal mechanisms that control the location and structure of the Nissl bodies.

Adjuvants, Immunologic↗