Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection

Abstract A major contribution to the burden of Tuberculosis (TB) comes from latent Mycobacterium tuberculosis infections (LTBI) becoming clinically active. TB and LTBI probably exist as a spectrum and currently there are no correlates available to identify individuals with LTBI most at risk of devel...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Matthew K. O’Shea, Rachel Tanner, Julius Müller, Stephanie A. Harris, Danny Wright, Lisa Stockdale, Elena Stylianou, Iman Satti, Steven G. Smith, James Dunbar, Thomas E. Fletcher, Martin Dedicoat, Adam F. Cunningham, Helen McShane
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Mycobacterial Growth Latent Mycobacterium Tuberculosis Infection (LTBI) IgG Response Mycobacterial Control Intermediate Monocytes Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3ef8d706e6048d38cfae23823929f5d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f3ef8d706e6048d38cfae23823929f5d
record_format	dspace
spelling	oai:doaj.org-article:f3ef8d706e6048d38cfae23823929f5d2021-12-02T15:09:03ZImmunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection10.1038/s41598-018-32755-x2045-2322https://doaj.org/article/f3ef8d706e6048d38cfae23823929f5d2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-32755-xhttps://doaj.org/toc/2045-2322Abstract A major contribution to the burden of Tuberculosis (TB) comes from latent Mycobacterium tuberculosis infections (LTBI) becoming clinically active. TB and LTBI probably exist as a spectrum and currently there are no correlates available to identify individuals with LTBI most at risk of developing active disease. We set out to identify immune parameters associated with ex vivo mycobacterial growth control among individuals with active TB disease or LTBI to define the spectrum of TB infection. We used a whole blood mycobacterial growth inhibition assay to generate a functional profile of growth control among individuals with TB, LTBI or uninfected controls. We subsequently used a multi-platform approach to identify an immune signature associated with this profile. We show, for the first time, that patients with active disease had the greatest control of mycobacterial growth, whilst there was a continuum of responses among latently infected patients, likely related to the degree of immune activation in response to bacillary load. Control correlated with multiple factors including inflammatory monocytes, activated and atypical memory B cells, IgG1 responses to TB-specific antigens and serum cytokines/chemokines. Our findings offer a method to stratify subclinical TB infections and the future potential to identify individuals most at risk of progressing to active disease and benefit from chemoprophylaxis.Matthew K. O’SheaRachel TannerJulius MüllerStephanie A. HarrisDanny WrightLisa StockdaleElena StylianouIman SattiSteven G. SmithJames DunbarThomas E. FletcherMartin DedicoatAdam F. CunninghamHelen McShaneNature PortfolioarticleMycobacterial GrowthLatent Mycobacterium Tuberculosis Infection (LTBI)IgG ResponseMycobacterial ControlIntermediate MonocytesMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mycobacterial Growth Latent Mycobacterium Tuberculosis Infection (LTBI) IgG Response Mycobacterial Control Intermediate Monocytes Medicine R Science Q
spellingShingle	Mycobacterial Growth Latent Mycobacterium Tuberculosis Infection (LTBI) IgG Response Mycobacterial Control Intermediate Monocytes Medicine R Science Q Matthew K. O’Shea Rachel Tanner Julius Müller Stephanie A. Harris Danny Wright Lisa Stockdale Elena Stylianou Iman Satti Steven G. Smith James Dunbar Thomas E. Fletcher Martin Dedicoat Adam F. Cunningham Helen McShane Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
description	Abstract A major contribution to the burden of Tuberculosis (TB) comes from latent Mycobacterium tuberculosis infections (LTBI) becoming clinically active. TB and LTBI probably exist as a spectrum and currently there are no correlates available to identify individuals with LTBI most at risk of developing active disease. We set out to identify immune parameters associated with ex vivo mycobacterial growth control among individuals with active TB disease or LTBI to define the spectrum of TB infection. We used a whole blood mycobacterial growth inhibition assay to generate a functional profile of growth control among individuals with TB, LTBI or uninfected controls. We subsequently used a multi-platform approach to identify an immune signature associated with this profile. We show, for the first time, that patients with active disease had the greatest control of mycobacterial growth, whilst there was a continuum of responses among latently infected patients, likely related to the degree of immune activation in response to bacillary load. Control correlated with multiple factors including inflammatory monocytes, activated and atypical memory B cells, IgG1 responses to TB-specific antigens and serum cytokines/chemokines. Our findings offer a method to stratify subclinical TB infections and the future potential to identify individuals most at risk of progressing to active disease and benefit from chemoprophylaxis.
format	article
author	Matthew K. O’Shea Rachel Tanner Julius Müller Stephanie A. Harris Danny Wright Lisa Stockdale Elena Stylianou Iman Satti Steven G. Smith James Dunbar Thomas E. Fletcher Martin Dedicoat Adam F. Cunningham Helen McShane
author_facet	Matthew K. O’Shea Rachel Tanner Julius Müller Stephanie A. Harris Danny Wright Lisa Stockdale Elena Stylianou Iman Satti Steven G. Smith James Dunbar Thomas E. Fletcher Martin Dedicoat Adam F. Cunningham Helen McShane
author_sort	Matthew K. O’Shea
title	Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
title_short	Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
title_full	Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
title_fullStr	Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
title_full_unstemmed	Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
title_sort	immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f3ef8d706e6048d38cfae23823929f5d
work_keys_str_mv	AT matthewkoshea immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT racheltanner immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT juliusmuller immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT stephanieaharris immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT dannywright immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT lisastockdale immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT elenastylianou immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT imansatti immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT stevengsmith immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT jamesdunbar immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT thomasefletcher immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT martindedicoat immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT adamfcunningham immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection AT helenmcshane immunologicalcorrelatesofmycobacterialgrowthinhibitiondescribeaspectrumoftuberculosisinfection
_version_	1718387975380795392

Immunological correlates of mycobacterial growth inhibition describe a spectrum of tuberculosis infection

Ejemplares similares