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

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 act...

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Vydáno v:Scientific reports Ročník 8; číslo 1; s. 14480 - 13
Hlavní autoři: O’Shea, Matthew K., Tanner, Rachel, Müller, Julius, Harris, Stephanie A., Wright, Danny, Stockdale, Lisa, Stylianou, Elena, Satti, Iman, Smith, Steven G., Dunbar, James, Fletcher, Thomas E., Dedicoat, Martin, Cunningham, Adam F., McShane, Helen
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 27.09.2018
Nature Publishing Group
Nature Portfolio
Témata:
13/1
13/21
13/31
631/250/255/1856
692/699/255/1856
Antigens
Chemokines
Cytokines
Humanities and Social Sciences
IgG Response
Immunoglobulin G
Immunological memory
Inflammation
Intermediate Monocytes
Latent infection
Latent Mycobacterium Tuberculosis Infection (LTBI)
Lymphocytes B
Memory cells
Monocytes
multidisciplinary
Mycobacterial Control
Mycobacterial Growth
Science
Science (multidisciplinary)
Tuberculosis
Mycobacterial Growth
IgG Response
Mycobacterial Control
Latent Mycobacterium Tuberculosis Infection (LTBI)
Intermediate Monocytes
ISSN:2045-2322, 2045-2322
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Shrnutí: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-32755-x