Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.
BACKGROUND:The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-...
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ftdoajarticles:oai:doaj.org/article:25fa656c16cd458cb027824d118c7cc2 2023-05-15T15:11:58+02:00 Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. Degang Yang Tiejun Shui Jake W Miranda Danny J Gilson Zhengyu Song Jia Chen Chao Shi Jianyu Zhu Jun Yang Zhichun Jing 2016-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004335 https://doaj.org/article/25fa656c16cd458cb027824d118c7cc2 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4713426?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004335 https://doaj.org/article/25fa656c16cd458cb027824d118c7cc2 PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004335 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004335 2022-12-31T11:55:31Z BACKGROUND:The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. METHODOLOGY/PRINCIPAL FINDINGS:Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. CONCLUSIONS/SIGNIFICANCE:Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 1 e0004335 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Degang Yang Tiejun Shui Jake W Miranda Danny J Gilson Zhengyu Song Jia Chen Chao Shi Jianyu Zhu Jun Yang Zhichun Jing Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:The persistence of Mycobacterium leprae (M. leprae) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M. leprae. We therefore postulated that M. leprae-infected macrophages might have altered immune functions. METHODOLOGY/PRINCIPAL FINDINGS:Here, we treated monocyte-derived macrophages with live or killed M. leprae, and examined their activation status and antigen presentation. We found that macrophages treated with live M. leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M. leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8+ T cell cytotoxicity were reduced. Chromium release assay also found that live M. leprae-treated macrophages were more resistant to CD8+ T cell-mediated cytotoxicity than sonicated M. leprae-treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. CONCLUSIONS/SIGNIFICANCE:Together, our data demonstrate that M. leprae could utilize infected macrophages by two mechanisms: firstly, M. leprae-infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M. leprae-infected macrophages were more effective at evading CD8+ T cell-mediated cytotoxicity. |
format |
Article in Journal/Newspaper |
author |
Degang Yang Tiejun Shui Jake W Miranda Danny J Gilson Zhengyu Song Jia Chen Chao Shi Jianyu Zhu Jun Yang Zhichun Jing |
author_facet |
Degang Yang Tiejun Shui Jake W Miranda Danny J Gilson Zhengyu Song Jia Chen Chao Shi Jianyu Zhu Jun Yang Zhichun Jing |
author_sort |
Degang Yang |
title |
Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. |
title_short |
Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. |
title_full |
Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. |
title_fullStr |
Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. |
title_full_unstemmed |
Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy. |
title_sort |
mycobacterium leprae-infected macrophages preferentially primed regulatory t cell responses and was associated with lepromatous leprosy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0004335 https://doaj.org/article/25fa656c16cd458cb027824d118c7cc2 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 1, p e0004335 (2016) |
op_relation |
http://europepmc.org/articles/PMC4713426?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004335 https://doaj.org/article/25fa656c16cd458cb027824d118c7cc2 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004335 |
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PLOS Neglected Tropical Diseases |
container_volume |
10 |
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1 |
container_start_page |
e0004335 |
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