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Bacterial Superantigen Toxins, CD28, and Drug Development
During severe bacterial infections, death and disease are often caused by an overly strong immune response of the human host. Acute toxic shock is induced by superantigen toxins, a diverse set of proteins secreted by Gram-positive staphylococcal and streptococcal bacterial strains that overstimulate...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265702/ https://www.ncbi.nlm.nih.gov/pubmed/30404186 http://dx.doi.org/10.3390/toxins10110459 |
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author | Kaempfer, Raymond |
author_facet | Kaempfer, Raymond |
author_sort | Kaempfer, Raymond |
collection | PubMed |
description | During severe bacterial infections, death and disease are often caused by an overly strong immune response of the human host. Acute toxic shock is induced by superantigen toxins, a diverse set of proteins secreted by Gram-positive staphylococcal and streptococcal bacterial strains that overstimulate the inflammatory response by orders of magnitude. The need to protect from superantigen toxins led to our discovery that in addition to the well-known MHC class II and T cell receptors, the principal costimulatory receptor, CD28, and its constitutively expressed coligand, B7-2 (CD86), previously thought to have only costimulatory function, are actually critical superantigen receptors. Binding of the superantigen into the homodimer interfaces of these costimulatory receptors greatly enhances B7-2/CD28 engagement, leading to excessive pro-inflammatory signaling. This finding led to the design of short receptor dimer interface mimetic peptides that block the binding of superantigen and thus protect from death. It then turned out that such a peptide will protect also from Gram-negative bacterial infection and from polymicrobial sepsis. One such CD28 mimetic peptide is advancing in a Phase 3 clinical trial to protect from lethal wound infections by flesh-eating bacteria. These host-oriented therapeutics target the human immune system itself, rendering pathogens less likely to become resistant. |
format | Online Article Text |
id | pubmed-6265702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62657022018-12-07 Bacterial Superantigen Toxins, CD28, and Drug Development Kaempfer, Raymond Toxins (Basel) Review During severe bacterial infections, death and disease are often caused by an overly strong immune response of the human host. Acute toxic shock is induced by superantigen toxins, a diverse set of proteins secreted by Gram-positive staphylococcal and streptococcal bacterial strains that overstimulate the inflammatory response by orders of magnitude. The need to protect from superantigen toxins led to our discovery that in addition to the well-known MHC class II and T cell receptors, the principal costimulatory receptor, CD28, and its constitutively expressed coligand, B7-2 (CD86), previously thought to have only costimulatory function, are actually critical superantigen receptors. Binding of the superantigen into the homodimer interfaces of these costimulatory receptors greatly enhances B7-2/CD28 engagement, leading to excessive pro-inflammatory signaling. This finding led to the design of short receptor dimer interface mimetic peptides that block the binding of superantigen and thus protect from death. It then turned out that such a peptide will protect also from Gram-negative bacterial infection and from polymicrobial sepsis. One such CD28 mimetic peptide is advancing in a Phase 3 clinical trial to protect from lethal wound infections by flesh-eating bacteria. These host-oriented therapeutics target the human immune system itself, rendering pathogens less likely to become resistant. MDPI 2018-11-06 /pmc/articles/PMC6265702/ /pubmed/30404186 http://dx.doi.org/10.3390/toxins10110459 Text en © 2018 by the author. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Kaempfer, Raymond Bacterial Superantigen Toxins, CD28, and Drug Development |
title | Bacterial Superantigen Toxins, CD28, and Drug Development |
title_full | Bacterial Superantigen Toxins, CD28, and Drug Development |
title_fullStr | Bacterial Superantigen Toxins, CD28, and Drug Development |
title_full_unstemmed | Bacterial Superantigen Toxins, CD28, and Drug Development |
title_short | Bacterial Superantigen Toxins, CD28, and Drug Development |
title_sort | bacterial superantigen toxins, cd28, and drug development |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265702/ https://www.ncbi.nlm.nih.gov/pubmed/30404186 http://dx.doi.org/10.3390/toxins10110459 |
work_keys_str_mv | AT kaempferraymond bacterialsuperantigentoxinscd28anddrugdevelopment |