IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy.
Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic in...
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ftdoajarticles:oai:doaj.org/article:239a2474aac1493c943ed5f99f7dca3e 2023-05-15T15:15:04+02:00 IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. Deanna A Hagge David M Scollard Nashone A Ray Vilma T Marks Angelina T Deming John S Spencer Linda B Adams 2014-09-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003149 https://doaj.org/article/239a2474aac1493c943ed5f99f7dca3e EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4161319?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003149 https://doaj.org/article/239a2474aac1493c943ed5f99f7dca3e PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3149 (2014) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2014 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003149 2022-12-31T12:14:15Z Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions.The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-), as well as mice deficient in both inducible nitric oxide synthase (NOS2-/-) and IL-10 (10NOS2-/-). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)<IL-10-/-<NOS2-/-<10NOS2-/-. While IL-10-/- mice exhibited modest FP induration compared to B6, NOS2-/- and 10NOS2-/- mice developed markedly enlarged FP marking distinct phases: early (1 month), peak (3-4 months), and chronic (8 months). IFN-γ-producing CD4+CD44+ cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B) were significantly increased in the evolved granuloma in NOS2-/- FP compared to B6 and IL-10-/- during early and peak phases. In 10NOS2-/- FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES), ML2038 (bacterioferritin), and ML1877 (EF-Tu). Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2-/- FP.The 10NOS2-/- strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 8 9 e3149 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Deanna A Hagge David M Scollard Nashone A Ray Vilma T Marks Angelina T Deming John S Spencer Linda B Adams IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions.The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10-/-), as well as mice deficient in both inducible nitric oxide synthase (NOS2-/-) and IL-10 (10NOS2-/-). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)<IL-10-/-<NOS2-/-<10NOS2-/-. While IL-10-/- mice exhibited modest FP induration compared to B6, NOS2-/- and 10NOS2-/- mice developed markedly enlarged FP marking distinct phases: early (1 month), peak (3-4 months), and chronic (8 months). IFN-γ-producing CD4+CD44+ cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B) were significantly increased in the evolved granuloma in NOS2-/- FP compared to B6 and IL-10-/- during early and peak phases. In 10NOS2-/- FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES), ML2038 (bacterioferritin), and ML1877 (EF-Tu). Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2-/- FP.The 10NOS2-/- strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the pathogenesis of neurological involvement. |
format |
Article in Journal/Newspaper |
author |
Deanna A Hagge David M Scollard Nashone A Ray Vilma T Marks Angelina T Deming John S Spencer Linda B Adams |
author_facet |
Deanna A Hagge David M Scollard Nashone A Ray Vilma T Marks Angelina T Deming John S Spencer Linda B Adams |
author_sort |
Deanna A Hagge |
title |
IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. |
title_short |
IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. |
title_full |
IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. |
title_fullStr |
IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. |
title_full_unstemmed |
IL-10 and NOS2 modulate antigen-specific reactivity and nerve infiltration by T cells in experimental leprosy. |
title_sort |
il-10 and nos2 modulate antigen-specific reactivity and nerve infiltration by t cells in experimental leprosy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2014 |
url |
https://doi.org/10.1371/journal.pntd.0003149 https://doaj.org/article/239a2474aac1493c943ed5f99f7dca3e |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3149 (2014) |
op_relation |
http://europepmc.org/articles/PMC4161319?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003149 https://doaj.org/article/239a2474aac1493c943ed5f99f7dca3e |
op_doi |
https://doi.org/10.1371/journal.pntd.0003149 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
8 |
container_issue |
9 |
container_start_page |
e3149 |
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