Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages

ABSTRACT During tuberculosis, macrophages are critical for both pathogen survival and host immune activation. Since expression of particular cell surface markers reflects cell function, we used flow cytometry to measure the abundance of surface markers associated with polarity, lipid uptake, or patt...

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Autores principales: Karim Lakehal, David Levine, Kathleen F. Kerr, Pooja Vir, Natalie Bruiners, Alfred Lardizabal, Maria Laura Gennaro, Richard Pine
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Publicado: American Society for Microbiology 2017
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spelling oai:doaj.org-article:54a18a8a646046b28c98667f0abe89982021-11-15T15:21:52ZTuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages10.1128/mSphere.00475-172379-5042https://doaj.org/article/54a18a8a646046b28c98667f0abe89982017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00475-17https://doaj.org/toc/2379-5042ABSTRACT During tuberculosis, macrophages are critical for both pathogen survival and host immune activation. Since expression of particular cell surface markers reflects cell function, we used flow cytometry to measure the abundance of surface markers associated with polarity, lipid uptake, or pattern recognition on macrophages found in induced sputum. Nine macrophage surface markers were examined from three groups of donors: infection-free, latent tuberculosis infection, and active pulmonary tuberculosis. Using a trend test, we found that expression of Toll-like receptor 2 was greater from absence of infection to latent infection and from latent infection to active tuberculosis. The results point to the possibility that innate immune cell phenotypes be used to distinguish among tuberculosis infection stages. Moreover, this study shows that readily accessible sputum macrophages have potential for tuberculosis diagnosis and prognosis. IMPORTANCE Mycobacterium tuberculosis is an intracellular pathogen that parasitizes the host macrophage. While approximately two billion people are infected worldwide, only 5 to 10% become diseased with pulmonary tuberculosis, at least in the absence of comorbidities. Tuberculosis control requires development of noninvasive methods probing the host immune status to help distinguish latent infection from active tuberculosis. With such methods, high-risk individuals could be targeted for treatment before disease manifestation. Previous investigations have been based on examination of peripheral blood cells or, more rarely, lung macrophages obtained with invasive procedures, such as bronchoalveolar lavages. Here we show that differences exist in the expression of a surface protein (Toll-like receptor 2) between macrophages recovered from the sputum of individuals in different diagnostic groups: i.e., infection free, latent tuberculosis infection, and active pulmonary tuberculosis. Thus, phenotypic analysis of local macrophages obtained with noninvasive procedures can help distinguish among tuberculosis infection stages.Karim LakehalDavid LevineKathleen F. KerrPooja VirNatalie BruinersAlfred LardizabalMaria Laura GennaroRichard PineAmerican Society for Microbiologyarticleimmunophenotypinginnate immunitymacrophage surface markerspattern recognition receptorstuberculosis biomarkersMicrobiologyQR1-502ENmSphere, Vol 2, Iss 6 (2017)
institution DOAJ
collection DOAJ
language EN
topic immunophenotyping
innate immunity
macrophage surface markers
pattern recognition receptors
tuberculosis biomarkers
Microbiology
QR1-502
spellingShingle immunophenotyping
innate immunity
macrophage surface markers
pattern recognition receptors
tuberculosis biomarkers
Microbiology
QR1-502
Karim Lakehal
David Levine
Kathleen F. Kerr
Pooja Vir
Natalie Bruiners
Alfred Lardizabal
Maria Laura Gennaro
Richard Pine
Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages
description ABSTRACT During tuberculosis, macrophages are critical for both pathogen survival and host immune activation. Since expression of particular cell surface markers reflects cell function, we used flow cytometry to measure the abundance of surface markers associated with polarity, lipid uptake, or pattern recognition on macrophages found in induced sputum. Nine macrophage surface markers were examined from three groups of donors: infection-free, latent tuberculosis infection, and active pulmonary tuberculosis. Using a trend test, we found that expression of Toll-like receptor 2 was greater from absence of infection to latent infection and from latent infection to active tuberculosis. The results point to the possibility that innate immune cell phenotypes be used to distinguish among tuberculosis infection stages. Moreover, this study shows that readily accessible sputum macrophages have potential for tuberculosis diagnosis and prognosis. IMPORTANCE Mycobacterium tuberculosis is an intracellular pathogen that parasitizes the host macrophage. While approximately two billion people are infected worldwide, only 5 to 10% become diseased with pulmonary tuberculosis, at least in the absence of comorbidities. Tuberculosis control requires development of noninvasive methods probing the host immune status to help distinguish latent infection from active tuberculosis. With such methods, high-risk individuals could be targeted for treatment before disease manifestation. Previous investigations have been based on examination of peripheral blood cells or, more rarely, lung macrophages obtained with invasive procedures, such as bronchoalveolar lavages. Here we show that differences exist in the expression of a surface protein (Toll-like receptor 2) between macrophages recovered from the sputum of individuals in different diagnostic groups: i.e., infection free, latent tuberculosis infection, and active pulmonary tuberculosis. Thus, phenotypic analysis of local macrophages obtained with noninvasive procedures can help distinguish among tuberculosis infection stages.
format article
author Karim Lakehal
David Levine
Kathleen F. Kerr
Pooja Vir
Natalie Bruiners
Alfred Lardizabal
Maria Laura Gennaro
Richard Pine
author_facet Karim Lakehal
David Levine
Kathleen F. Kerr
Pooja Vir
Natalie Bruiners
Alfred Lardizabal
Maria Laura Gennaro
Richard Pine
author_sort Karim Lakehal
title Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages
title_short Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages
title_full Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages
title_fullStr Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages
title_full_unstemmed Tuberculosis State Is Associated with Expression of Toll-Like Receptor 2 in Sputum Macrophages
title_sort tuberculosis state is associated with expression of toll-like receptor 2 in sputum macrophages
publisher American Society for Microbiology
publishDate 2017
url https://doaj.org/article/54a18a8a646046b28c98667f0abe8998
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