Immune modulation by the cholera-like enterotoxins: from adjuvant to therapeutic

Williams, Neil; Hirst, Timothy R.; Nashar, Toufic O.

doi:10.1016/s0167-5699(98)01397-8

Cited by 205 publications

(149 citation statements)

References 55 publications

Supporting

Mentioning

144

Contrasting

Unclassified

Order By: Relevance

“…Binding of CT, LT-I, and LT-IIa, but not binding of LT-IIb, to CD8 ϩ T cells induces apoptosis (2,58). Binding of CT or LT-I to B cells leads to polyclonal activation and to upregulated expression of MHC-II, B7, CD40, CD80, CD86, ICAM-1, and IL-2R␣ (2,36,41).…”

Section: Discussionmentioning

confidence: 99%

Mutants of Type II Heat-Labile Enterotoxin LT-IIa with Altered Ganglioside-Binding Activities and Diminished Toxicity Are Potent Mucosal Adjuvants

et al. 2007

View full text Add to dashboard Cite

The structure and function LT-IIa, a type II heat-labile enterotoxin of Escherichia coli, are closely related to the structures and functions of cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. While LT-IIa is a potent systemic and mucosal adjuvant, recent studies demonstrated that mutant LT-IIa(T34I), which exhibits no detectable binding activity as determined by an enzyme-linked immunosorbent assay, with gangliosides GD1b, GD1a, and GM1 is a very poor adjuvant.

show abstract

Section: Discussionmentioning

confidence: 99%

Mutants of Type II Heat-Labile Enterotoxin LT-IIa with Altered Ganglioside-Binding Activities and Diminished Toxicity Are Potent Mucosal Adjuvants

et al. 2007

View full text Add to dashboard Cite

show abstract

“…This is quite interesting since oral adjuvants have to survive the harsh gastric environment and avoid destruction from pancreatic proteases. Accordingly, bacterial toxins are generally more effective mucosal adjuvants following nasotracheal administration than following oral administration (38,54) (Fig. 3 to 5).…”

Section: Discussionmentioning

confidence: 99%

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

et al. 2004

View full text Add to dashboard Cite

The receptor binding domains of the most potent mucosal adjuvants, bacterial toxins and plant lectins, are organized in repeat units to recognize specific sugar residues. The lectin-like structure of the C-terminal region of Clostridium difficile toxin A prompted us to investigate the mucosal adjuvant properties of a nontoxigenic peptide corresponding to amino acids 2394 to 2706 (TxA C314 ). We compared TxA C314 adjuvant activity to those of cholera toxin (

show abstract

“…Cholera toxin (CT) has a strong adjuvant effect [15]. When administered in the mucosa, CT can elicit a Th2-type response that is based on the production of IL-4, IL-5 and IL-10 but virtually no 17].…”

mentioning

confidence: 99%

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

et al. 2011

View full text Add to dashboard Cite

The nature of CD4 1 T-cell responses after skin immunization and the role of migrating DCs in the presence of adjuvants in the elicited response are interesting issues to be investigated. Here, we evaluated the priming of CD4 1 T cells following ear immunization with low doses of model antigens in combination with either cholera toxin (CT) or the non-toxic b CT subunit (CTB) as an adjuvant. Following immunization with CT, we found efficient antigen presentation that is reflected in the production of IFN-c and IL-17 by CD4 1 T cells over IL-4 or IL-5 production. The CTB-induced activation of DCs in the ear occurred without visible inflammation, which reflects a similar type of CD4 1 T-cell differentiation. In both cases, the elicited response was dependent on the presence of migrating skin cells. Remarkably, immunization with CT or with CTB led to the induction of a delayed-type hypersensitivity (DTH) response in the ear. The DTH response that was induced by CT immunization was dependent on IL-17 and partially dependent on IFN-c activity. These results indicate that both CT and CTB induce an efficient CD4 1 T-cell response to a co-administered antigen following ear immunization that is dependent on migrating DCs.Key words: DCs . Migrating DCs . Skin immunization Supporting Information available online IntroductionThe skin is the first line of defense against microbial pathogens. There is supporting evidence that DCs are crucial for the initiation, polarization and control of the adaptive immune response [1,2]. Efficient immunosurveillance in the skin is based upon the continuous traffic of cells from the skin to the draining lymph nodes. Although Langerhans cells (LCs) have been shown to be potent APCs in vitro [3], in vivo approaches have produced conflicting data regarding their role in T-cell priming [4,5]. Dermal DCs are also migrating DCs that colonize lymph nodes more rapidly than LCs [6,7], and different roles for skin DC subsets in T-cell priming have been reported [7][8][9]. Skin immunization has yielded controversial data, with some reports supporting a Th2-type response [10,11] and others a Th1-type response [12,13]. IL-17-producing CD4 1 T cells (Th17) have also been found after skin immunization [13,14]. 2894Cholera toxin (CT) has a strong adjuvant effect [15]. When administered in the mucosa, CT can elicit a Th2-type response that is based on the production of IL-4, IL-5 and IL-10 but virtually no 17]. However, a mixed Th1/Th2 response that produces both IFN-g and IL-4 has also been observed [18], and the administration of ovalbumin (OVA) in combination with CT elicits a dominant Th17 response following intranasal immunization [19]. This dominance of IL-17 was also observed in response to the CT b subunit (CTB). Although the precise mechanism for the adjuvant effect of CT is not completely understood, it appears that CTB targets DCs in vivo by binding to the cell membrane ganglioside GM1 [20]; moreover, the CT a subunit (CTA) triggers the PKA-mediated induction of cAMP, which plays a critical role ...

show abstract

Immune modulation by the cholera-like enterotoxins: from adjuvant to therapeutic

Cited by 205 publications

References 55 publications

Mutants of Type II Heat-Labile Enterotoxin LT-IIa with Altered Ganglioside-Binding Activities and Diminished Toxicity Are Potent Mucosal Adjuvants

Mutants of Type II Heat-Labile Enterotoxin LT-IIa with Altered Ganglioside-Binding Activities and Diminished Toxicity Are Potent Mucosal Adjuvants

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

Intradermal immunization in the ear with cholera toxin and its non‐toxic β subunit promotes efficient Th1 and Th17 differentiation dependent on migrating DCs

Contact Info

Product

Resources

About