Parallels between pathogens and gluten peptides in celiac sprue.

Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dieta...

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Autores principales:	Michael T Bethune, Chaitan Khosla
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f4d9dcf3efe940ceafeb3b70bba7ef01
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spelling	oai:doaj.org-article:f4d9dcf3efe940ceafeb3b70bba7ef012021-11-25T05:46:42ZParallels between pathogens and gluten peptides in celiac sprue.1553-73661553-737410.1371/journal.ppat.0040034https://doaj.org/article/f4d9dcf3efe940ceafeb3b70bba7ef012008-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18425213/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell-mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights.Michael T BethuneChaitan KhoslaPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 4, Iss 2, p e34 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Michael T Bethune Chaitan Khosla Parallels between pathogens and gluten peptides in celiac sprue.
description	Pathogens are exogenous agents capable of causing disease in susceptible organisms. In celiac sprue, a disease triggered by partially hydrolyzed gluten peptides in the small intestine, the offending immunotoxins cannot replicate, but otherwise have many hallmarks of classical pathogens. First, dietary gluten and its peptide metabolites are ubiquitous components of the modern diet, yet only a small, genetically susceptible fraction of the human population contracts celiac sprue. Second, immunotoxic gluten peptides have certain unusual structural features that allow them to survive the harsh proteolytic conditions of the gastrointestinal tract and thereby interact extensively with the mucosal lining of the small intestine. Third, they invade across epithelial barriers intact to access the underlying gut-associated lymphoid tissue. Fourth, they possess recognition sequences for selective modification by an endogenous enzyme, transglutaminase 2, allowing for in situ activation to a more immunotoxic form via host subversion. Fifth, they precipitate a T cell-mediated immune reaction comprising both innate and adaptive responses that causes chronic inflammation of the small intestine. Sixth, complete elimination of immunotoxic gluten peptides from the celiac diet results in remission, whereas reintroduction of gluten in the diet causes relapse. Therefore, in analogy with antibiotics, orally administered proteases that reduce the host's exposure to the immunotoxin by accelerating gluten peptide destruction have considerable therapeutic potential. Last but not least, notwithstanding the power of in vitro methods to reconstitute the essence of the immune response to gluten in a celiac patient, animal models for the disease, while elusive, are likely to yield fundamentally new systems-level insights.
format	article
author	Michael T Bethune Chaitan Khosla
author_facet	Michael T Bethune Chaitan Khosla
author_sort	Michael T Bethune
title	Parallels between pathogens and gluten peptides in celiac sprue.
title_short	Parallels between pathogens and gluten peptides in celiac sprue.
title_full	Parallels between pathogens and gluten peptides in celiac sprue.
title_fullStr	Parallels between pathogens and gluten peptides in celiac sprue.
title_full_unstemmed	Parallels between pathogens and gluten peptides in celiac sprue.
title_sort	parallels between pathogens and gluten peptides in celiac sprue.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/f4d9dcf3efe940ceafeb3b70bba7ef01
work_keys_str_mv	AT michaeltbethune parallelsbetweenpathogensandglutenpeptidesinceliacsprue AT chaitankhosla parallelsbetweenpathogensandglutenpeptidesinceliacsprue
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Parallels between pathogens and gluten peptides in celiac sprue.

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