Effects of cholera toxin on innate and adaptive immunity and its application as an immunomodulatory agent

Lavelle, Ed C.; Jarnicki, Andrew G.; McNeela, Edel A.; Armstrong, Michelle E.; Higgins, Sarah C.; Leavy, Olive; Mills, Kingston H. G.

doi:10.1189/jlb.1103534

Cited by 91 publications

(87 citation statements)

References 71 publications

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“…All nucleated cells, including all professional APCs, can bind the toxins via the GM1 ganglioside receptor present in the cell membrane. Previous reports have documented both proinflammatory and anti-inflammatory effects of CT. From several studies, including our own work, it has been demonstrated that CT exposure of APCs has an augmenting effect on IL-1 and IL-6 production, whereas other studies have reported a downregulating effect on IL-12 and TNF-a, and a promoting effect on IL-10 and IL-17 production [35,[48][49][50][51]. Taken together, these effects would indicate both a proinflammatory and an anti-inflammatory function of CT on innate immunity.…”

Section: The Cta1-dd Adjuvant Effectively Promotes Long-lived Plasma mentioning

confidence: 82%

Is the choice of vaccine adjuvant critical for long-term memory development?

Lycke¹

2010

Expert Review of Vaccines

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Section: The Cta1-dd Adjuvant Effectively Promotes Long-lived Plasma mentioning

confidence: 82%

Is the choice of vaccine adjuvant critical for long-term memory development?

Lycke¹

2010

Expert Review of Vaccines

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“…It has previously been shown that Ctx confers stimulatory effects through DC in some experimental settings [18,19,26], and tolerogenic effects in others [28,29]. This is possibly related to the activation and maturation stage of the DC at the time they encounter the Ctx.…”

Section: Discussionmentioning

confidence: 98%

“…It can also be used for bait vaccination Cholera toxin (Ctx) is a potent mucosal adjuvant that has been used successfully in a large number of murine studies [10,13,14,29]. Unfortunately, the high toxicity of native Ctx in humans precludes the clinical use of Ctx [32].…”

Section: Introductionmentioning

confidence: 99%

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Cholera toxin promotes the generation of semi-mature porcine monocyte-derived dendritic cells that are unable to stimulate T cells

et al. 2007

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-Cholera toxin (Ctx) is a powerful mucosal adjuvant with potential applications for oral vaccination of swine. Dendritic cells (DC) play a key role in the decision between immunity and tolerance, and are likely target cells for mediating Ctx functions in vivo. Therefore, we examined the capacity of Ctx to enhance stimulatory activity of porcine monocyte-derived DC (MoDC). Ctx promoted the development of a semi-mature DC phenotype, with decreased levels of MHC class II and CD40, but increased CD80/86 expression. These changes were associated with activation of extracellular signal-regulated kinase (ERK), but not NFκB or c-Jun N-terminal kinase (JNK). Functionally, Ctx-priming greatly diminished T cell stimulatory capacity both in antigen-specific and superantigen-induced proliferation assays. The lower proliferation rate was not due to increased apoptosis of either DC or T cells. Ctx suppressed TNFα secretion by MoDC, but induced IL-10 production. The observed effects on T cell proliferation could only be partially mimicked by IL-10 alone. However, addition of recombinant TNFα to co-cultures of Ctx-primed MoDC and lymphocytes restored lymphocyte proliferation in a concentration-dependent manner. Ctx-primed DC were not actively tolerogenic, since they could not suppress proliferative T cell reactions induced by untreated DC. pig / dendritic cell / cholera toxin / adjuvant

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“…CT's mode of pathogenic action has been well characterized (14,15). The bulk of research now focuses more on its powerful immune response adjuvant and immunomodulating properties (15,16). Orally introduced CT in low, non-pathogenic doses alters gut mucosal immunity and effectively enhances the induction of antigen-specific oral tolerance (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%