EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.

Understanding host defense against microbes is key to developing new and more effective therapies for infection and inflammatory disease. However, how animals integrate multiple environmental signals and discriminate between different pathogens to mount specific and tailored responses remains poorly...

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Autores principales:	Lyly G Luhachack, Orane Visvikis, Amanda C Wollenberg, Adam Lacy-Hulbert, Lynda M Stuart, Javier E Irazoqui
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f086950cbd784a35afe744de2f788c99
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spelling	oai:doaj.org-article:f086950cbd784a35afe744de2f788c992021-11-18T06:04:14ZEGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.1553-73661553-737410.1371/journal.ppat.1002798https://doaj.org/article/f086950cbd784a35afe744de2f788c992012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22792069/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Understanding host defense against microbes is key to developing new and more effective therapies for infection and inflammatory disease. However, how animals integrate multiple environmental signals and discriminate between different pathogens to mount specific and tailored responses remains poorly understood. Using the genetically tractable model host Caenorhabditis elegans and pathogenic bacterium Staphylococcus aureus, we describe an important role for hypoxia-inducible factor (HIF) in defining the specificity of the host response in the intestine. We demonstrate that loss of egl-9, a negative regulator of HIF, confers HIF-dependent enhanced susceptibility to S. aureus while increasing resistance to Pseudomonas aeruginosa. In our attempt to understand how HIF could have these apparently dichotomous roles in host defense, we find that distinct pathways separately regulate two opposing functions of HIF: the canonical pathway is important for blocking expression of a set of HIF-induced defense genes, whereas a less well understood noncanonical pathway appears to be important for allowing the expression of another distinct set of HIF-repressed defense genes. Thus, HIF can function either as a gene-specific inducer or repressor of host defense, providing a molecular mechanism by which HIF can have apparently opposing roles in defense and inflammation. Together, our observations show that HIF can set the balance between alternative pathogen-specific host responses, potentially acting as an evolutionarily conserved specificity switch in the host innate immune response.Lyly G LuhachackOrane VisvikisAmanda C WollenbergAdam Lacy-HulbertLynda M StuartJavier E IrazoquiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 7, p e1002798 (2012)
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 Lyly G Luhachack Orane Visvikis Amanda C Wollenberg Adam Lacy-Hulbert Lynda M Stuart Javier E Irazoqui EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.
description	Understanding host defense against microbes is key to developing new and more effective therapies for infection and inflammatory disease. However, how animals integrate multiple environmental signals and discriminate between different pathogens to mount specific and tailored responses remains poorly understood. Using the genetically tractable model host Caenorhabditis elegans and pathogenic bacterium Staphylococcus aureus, we describe an important role for hypoxia-inducible factor (HIF) in defining the specificity of the host response in the intestine. We demonstrate that loss of egl-9, a negative regulator of HIF, confers HIF-dependent enhanced susceptibility to S. aureus while increasing resistance to Pseudomonas aeruginosa. In our attempt to understand how HIF could have these apparently dichotomous roles in host defense, we find that distinct pathways separately regulate two opposing functions of HIF: the canonical pathway is important for blocking expression of a set of HIF-induced defense genes, whereas a less well understood noncanonical pathway appears to be important for allowing the expression of another distinct set of HIF-repressed defense genes. Thus, HIF can function either as a gene-specific inducer or repressor of host defense, providing a molecular mechanism by which HIF can have apparently opposing roles in defense and inflammation. Together, our observations show that HIF can set the balance between alternative pathogen-specific host responses, potentially acting as an evolutionarily conserved specificity switch in the host innate immune response.
format	article
author	Lyly G Luhachack Orane Visvikis Amanda C Wollenberg Adam Lacy-Hulbert Lynda M Stuart Javier E Irazoqui
author_facet	Lyly G Luhachack Orane Visvikis Amanda C Wollenberg Adam Lacy-Hulbert Lynda M Stuart Javier E Irazoqui
author_sort	Lyly G Luhachack
title	EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.
title_short	EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.
title_full	EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.
title_fullStr	EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.
title_full_unstemmed	EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.
title_sort	egl-9 controls c. elegans host defense specificity through prolyl hydroxylation-dependent and -independent hif-1 pathways.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/f086950cbd784a35afe744de2f788c99
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EGL-9 controls C. elegans host defense specificity through prolyl hydroxylation-dependent and -independent HIF-1 pathways.

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