High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids

Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or le...

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Autores principales:	Carolina S. Silva, Christopher Sundling, Elin Folkesson, Gabrielle Fröberg, Claudia Nobrega, João Canto-Gomes, Benedict J. Chambers, Tadepally Lakshmikanth, Petter Brodin, Judith Bruchfeld, Jérôme Nigou, Margarida Correia-Neves, Gunilla Källenius
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tuberculosis mycobacterial glycolipids active tuberculosis (ATB) latent tuberculosis (LTB) hyporesponsiveness lipoarabinomannan (LAM) Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/fa96c632e81d4eb29b1785a92977feef
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spelling	oai:doaj.org-article:fa96c632e81d4eb29b1785a92977feef2021-11-30T14:34:25ZHigh Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids1664-322410.3389/fimmu.2021.727300https://doaj.org/article/fa96c632e81d4eb29b1785a92977feef2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.727300/fullhttps://doaj.org/toc/1664-3224Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.Carolina S. SilvaCarolina S. SilvaChristopher SundlingChristopher SundlingElin FolkessonElin FolkessonGabrielle FröbergGabrielle FröbergClaudia NobregaClaudia NobregaJoão Canto-GomesJoão Canto-GomesBenedict J. ChambersTadepally LakshmikanthPetter BrodinPetter BrodinJudith BruchfeldJudith BruchfeldJérôme NigouMargarida Correia-NevesMargarida Correia-NevesMargarida Correia-NevesGunilla KälleniusFrontiers Media S.A.articletuberculosismycobacterial glycolipidsactive tuberculosis (ATB)latent tuberculosis (LTB)hyporesponsivenesslipoarabinomannan (LAM)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tuberculosis mycobacterial glycolipids active tuberculosis (ATB) latent tuberculosis (LTB) hyporesponsiveness lipoarabinomannan (LAM) Immunologic diseases. Allergy RC581-607
spellingShingle	tuberculosis mycobacterial glycolipids active tuberculosis (ATB) latent tuberculosis (LTB) hyporesponsiveness lipoarabinomannan (LAM) Immunologic diseases. Allergy RC581-607 Carolina S. Silva Carolina S. Silva Christopher Sundling Christopher Sundling Elin Folkesson Elin Folkesson Gabrielle Fröberg Gabrielle Fröberg Claudia Nobrega Claudia Nobrega João Canto-Gomes João Canto-Gomes Benedict J. Chambers Tadepally Lakshmikanth Petter Brodin Petter Brodin Judith Bruchfeld Judith Bruchfeld Jérôme Nigou Margarida Correia-Neves Margarida Correia-Neves Margarida Correia-Neves Gunilla Källenius High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
description	Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.
format	article
author	Carolina S. Silva Carolina S. Silva Christopher Sundling Christopher Sundling Elin Folkesson Elin Folkesson Gabrielle Fröberg Gabrielle Fröberg Claudia Nobrega Claudia Nobrega João Canto-Gomes João Canto-Gomes Benedict J. Chambers Tadepally Lakshmikanth Petter Brodin Petter Brodin Judith Bruchfeld Judith Bruchfeld Jérôme Nigou Margarida Correia-Neves Margarida Correia-Neves Margarida Correia-Neves Gunilla Källenius
author_facet	Carolina S. Silva Carolina S. Silva Christopher Sundling Christopher Sundling Elin Folkesson Elin Folkesson Gabrielle Fröberg Gabrielle Fröberg Claudia Nobrega Claudia Nobrega João Canto-Gomes João Canto-Gomes Benedict J. Chambers Tadepally Lakshmikanth Petter Brodin Petter Brodin Judith Bruchfeld Judith Bruchfeld Jérôme Nigou Margarida Correia-Neves Margarida Correia-Neves Margarida Correia-Neves Gunilla Källenius
author_sort	Carolina S. Silva
title	High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
title_short	High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
title_full	High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
title_fullStr	High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
title_full_unstemmed	High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids
title_sort	high dimensional immune profiling reveals different response patterns in active and latent tuberculosis following stimulation with mycobacterial glycolipids
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/fa96c632e81d4eb29b1785a92977feef
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High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids

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