Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Katherine J Kasper, Joseph J Zeppa, Adrienne T Wakabayashi, Stacey X Xu, Delfina M Mazzuca, Ian Welch, Miren L Baroja, Malak Kotb, Ewa Cairns, P Patrick Cleary, S M Mansour Haeryfar, John K McCormick
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ac1b66d7d94a4ec6aeab4da369e8e0a4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ac1b66d7d94a4ec6aeab4da369e8e0a4
record_format	dspace
spelling	oai:doaj.org-article:ac1b66d7d94a4ec6aeab4da369e8e0a42021-11-11T06:06:13ZBacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.1553-73661553-737410.1371/journal.ppat.1004155https://doaj.org/article/ac1b66d7d94a4ec6aeab4da369e8e0a42014-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24875883/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.Katherine J KasperJoseph J ZeppaAdrienne T WakabayashiStacey X XuDelfina M MazzucaIan WelchMiren L BarojaMalak KotbEwa CairnsP Patrick ClearyS M Mansour HaeryfarJohn K McCormickPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 5, p e1004155 (2014)
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 Katherine J Kasper Joseph J Zeppa Adrienne T Wakabayashi Stacey X Xu Delfina M Mazzuca Ian Welch Miren L Baroja Malak Kotb Ewa Cairns P Patrick Cleary S M Mansour Haeryfar John K McCormick Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.
description	Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibility complex (MHC-II) molecules. S. pyogenes invariably encodes multiple SAgs, often within putative mobile genetic elements, and although SAgs are documented virulence factors for diseases such as scarlet fever and the streptococcal toxic shock syndrome (STSS), how these exotoxins contribute to the fitness and evolution of S. pyogenes is unknown. Here we show that acute infection in the nasopharynx is dependent upon both bacterial SAgs and host MHC-II molecules. S. pyogenes was rapidly cleared from the nasal cavity of wild-type C57BL/6 (B6) mice, whereas infection was enhanced up to ∼10,000-fold in B6 mice that express human MHC-II. This phenotype required the SpeA superantigen, and vaccination with an MHC -II binding mutant toxoid of SpeA dramatically inhibited infection. Our findings indicate that streptococcal SAgs are critical for the establishment of nasopharyngeal infection, thus providing an explanation as to why S. pyogenes produces these potent toxins. This work also highlights that SAg redundancy exists to avoid host anti-SAg humoral immune responses and to potentially overcome host MHC-II polymorphisms.
format	article
author	Katherine J Kasper Joseph J Zeppa Adrienne T Wakabayashi Stacey X Xu Delfina M Mazzuca Ian Welch Miren L Baroja Malak Kotb Ewa Cairns P Patrick Cleary S M Mansour Haeryfar John K McCormick
author_facet	Katherine J Kasper Joseph J Zeppa Adrienne T Wakabayashi Stacey X Xu Delfina M Mazzuca Ian Welch Miren L Baroja Malak Kotb Ewa Cairns P Patrick Cleary S M Mansour Haeryfar John K McCormick
author_sort	Katherine J Kasper
title	Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.
title_short	Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.
title_full	Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.
title_fullStr	Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.
title_full_unstemmed	Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.
title_sort	bacterial superantigens promote acute nasopharyngeal infection by streptococcus pyogenes in a human mhc class ii-dependent manner.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/ac1b66d7d94a4ec6aeab4da369e8e0a4
work_keys_str_mv	AT katherinejkasper bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT josephjzeppa bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT adriennetwakabayashi bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT staceyxxu bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT delfinammazzuca bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT ianwelch bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT mirenlbaroja bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT malakkotb bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT ewacairns bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT ppatrickcleary bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT smmansourhaeryfar bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner AT johnkmccormick bacterialsuperantigenspromoteacutenasopharyngealinfectionbystreptococcuspyogenesinahumanmhcclassiidependentmanner
_version_	1718439525724717056

Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

Ejemplares similares