Persistently active microbial molecules prolong innate immune tolerance in vivo.

Measures that bolster the resolution phase of infectious diseases may offer new opportunities for improving outcome. Here we show that inactivation of microbial lipopolysaccharides (LPS) can be required for animals to recover from the innate immune tolerance that follows exposure to Gram-negative ba...

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Autores principales:	Mingfang Lu, Alan W Varley, Robert S Munford
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c86d646c469242e2a251204ec9bb3a19
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spelling	oai:doaj.org-article:c86d646c469242e2a251204ec9bb3a192021-11-18T06:05:40ZPersistently active microbial molecules prolong innate immune tolerance in vivo.1553-73661553-737410.1371/journal.ppat.1003339https://doaj.org/article/c86d646c469242e2a251204ec9bb3a192013-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23675296/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Measures that bolster the resolution phase of infectious diseases may offer new opportunities for improving outcome. Here we show that inactivation of microbial lipopolysaccharides (LPS) can be required for animals to recover from the innate immune tolerance that follows exposure to Gram-negative bacteria. When wildtype mice are exposed to small parenteral doses of LPS or Gram-negative bacteria, their macrophages become reprogrammed (tolerant) for a few days before they resume normal function. Mice that are unable to inactivate LPS, in contrast, remain tolerant for several months; during this time they respond sluggishly to Gram-negative bacterial challenge, with high mortality. We show here that prolonged macrophage reprogramming is maintained in vivo by the persistence of stimulatory LPS molecules within the cells' in vivo environment, where naïve cells can acquire LPS via cell-cell contact or from the extracellular fluid. The findings provide strong evidence that inactivation of a stimulatory microbial molecule can be required for animals to regain immune homeostasis following parenteral exposure to bacteria. Measures that disable microbial molecules might enhance resolution of tissue inflammation and help restore innate defenses in individuals recovering from many different infectious diseases.Mingfang LuAlan W VarleyRobert S MunfordPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 5, p e1003339 (2013)
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 Mingfang Lu Alan W Varley Robert S Munford Persistently active microbial molecules prolong innate immune tolerance in vivo.
description	Measures that bolster the resolution phase of infectious diseases may offer new opportunities for improving outcome. Here we show that inactivation of microbial lipopolysaccharides (LPS) can be required for animals to recover from the innate immune tolerance that follows exposure to Gram-negative bacteria. When wildtype mice are exposed to small parenteral doses of LPS or Gram-negative bacteria, their macrophages become reprogrammed (tolerant) for a few days before they resume normal function. Mice that are unable to inactivate LPS, in contrast, remain tolerant for several months; during this time they respond sluggishly to Gram-negative bacterial challenge, with high mortality. We show here that prolonged macrophage reprogramming is maintained in vivo by the persistence of stimulatory LPS molecules within the cells' in vivo environment, where naïve cells can acquire LPS via cell-cell contact or from the extracellular fluid. The findings provide strong evidence that inactivation of a stimulatory microbial molecule can be required for animals to regain immune homeostasis following parenteral exposure to bacteria. Measures that disable microbial molecules might enhance resolution of tissue inflammation and help restore innate defenses in individuals recovering from many different infectious diseases.
format	article
author	Mingfang Lu Alan W Varley Robert S Munford
author_facet	Mingfang Lu Alan W Varley Robert S Munford
author_sort	Mingfang Lu
title	Persistently active microbial molecules prolong innate immune tolerance in vivo.
title_short	Persistently active microbial molecules prolong innate immune tolerance in vivo.
title_full	Persistently active microbial molecules prolong innate immune tolerance in vivo.
title_fullStr	Persistently active microbial molecules prolong innate immune tolerance in vivo.
title_full_unstemmed	Persistently active microbial molecules prolong innate immune tolerance in vivo.
title_sort	persistently active microbial molecules prolong innate immune tolerance in vivo.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c86d646c469242e2a251204ec9bb3a19
work_keys_str_mv	AT mingfanglu persistentlyactivemicrobialmoleculesprolonginnateimmunetoleranceinvivo AT alanwvarley persistentlyactivemicrobialmoleculesprolonginnateimmunetoleranceinvivo AT robertsmunford persistentlyactivemicrobialmoleculesprolonginnateimmunetoleranceinvivo
_version_	1718424631921082368

Persistently active microbial molecules prolong innate immune tolerance in vivo.

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