Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jill K Terra, Bryan France, Christopher K Cote, Amy Jenkins, Joel A Bozue, Susan L Welkos, Ragini Bhargava, Chi-Lee Ho, Margarete Mehrabian, Calvin Pan, Aldons J Lusis, Richard C Davis, Steven M LeVine, Kenneth A Bradley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/268629d88df4443393b3b819c4cfb5ee
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:268629d88df4443393b3b819c4cfb5ee
record_format	dspace
spelling	oai:doaj.org-article:268629d88df4443393b3b819c4cfb5ee2021-11-18T06:04:55ZAllelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.1553-73661553-737410.1371/journal.ppat.1002469https://doaj.org/article/268629d88df4443393b3b819c4cfb5ee2011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22241984/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.Jill K TerraBryan FranceChristopher K CoteAmy JenkinsJoel A BozueSusan L WelkosRagini BhargavaChi-Lee HoMargarete MehrabianCalvin PanAldons J LusisRichard C DavisSteven M LeVineKenneth A BradleyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 12, p e1002469 (2011)
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 Jill K Terra Bryan France Christopher K Cote Amy Jenkins Joel A Bozue Susan L Welkos Ragini Bhargava Chi-Lee Ho Margarete Mehrabian Calvin Pan Aldons J Lusis Richard C Davis Steven M LeVine Kenneth A Bradley Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.
description	Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.
format	article
author	Jill K Terra Bryan France Christopher K Cote Amy Jenkins Joel A Bozue Susan L Welkos Ragini Bhargava Chi-Lee Ho Margarete Mehrabian Calvin Pan Aldons J Lusis Richard C Davis Steven M LeVine Kenneth A Bradley
author_facet	Jill K Terra Bryan France Christopher K Cote Amy Jenkins Joel A Bozue Susan L Welkos Ragini Bhargava Chi-Lee Ho Margarete Mehrabian Calvin Pan Aldons J Lusis Richard C Davis Steven M LeVine Kenneth A Bradley
author_sort	Jill K Terra
title	Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.
title_short	Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.
title_full	Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.
title_fullStr	Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.
title_full_unstemmed	Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.
title_sort	allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to bacillus anthracis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/268629d88df4443393b3b819c4cfb5ee
work_keys_str_mv	AT jillkterra allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT bryanfrance allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT christopherkcote allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT amyjenkins allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT joelabozue allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT susanlwelkos allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT raginibhargava allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT chileeho allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT margaretemehrabian allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT calvinpan allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT aldonsjlusis allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT richardcdavis allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT stevenmlevine allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis AT kennethabradley allelicvariationonmurinechromosome11modifieshostinflammatoryresponsesandresistancetobacillusanthracis
_version_	1718424589911982080

Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

Ejemplares similares