Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions.
BACKGROUND:Leprosy, a chronic granulomatous disease affecting the skin and nerves, is caused by Mycobacterium leprae (M. leprae). The type of leprosy developed depends upon the host immune response. Type 1 reactions (T1Rs), that complicate borderline and lepromatous leprosy, are due to an increase i...
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ftdoajarticles:oai:doaj.org/article:e2a50e6795644c7bb418591eb87bb2c6 2023-05-15T15:10:52+02:00 Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. Anna L Cogen Stephen L Walker Chrissy H Roberts Deanna A Hagge Kapil D Neupane Saraswoti Khadge Diana N J Lockwood 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001869 https://doaj.org/article/e2a50e6795644c7bb418591eb87bb2c6 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3486878?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001869 https://doaj.org/article/e2a50e6795644c7bb418591eb87bb2c6 PLoS Neglected Tropical Diseases, Vol 6, Iss 11, p e1869 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001869 2022-12-31T13:05:48Z BACKGROUND:Leprosy, a chronic granulomatous disease affecting the skin and nerves, is caused by Mycobacterium leprae (M. leprae). The type of leprosy developed depends upon the host immune response. Type 1 reactions (T1Rs), that complicate borderline and lepromatous leprosy, are due to an increase in cell-mediated immunity and manifest as nerve damage and skin inflammation. Owing to the increase in inflammation in the skin of patients with T1Rs, we sought to investigate the activation of the innate immune system during reactionary events. Specifically, we investigated the expression levels of human beta-defensins (hBDs) 2 and 3 in the skin of patients with T1Rs, in keratinocytes, and in macrophages stimulated with M. leprae and corticosteroids. RESULTS:Skin biopsies from twenty-three patients with Type 1 reactions were found to have higher transcript levels of hBD3 as compared to fifteen leprosy patients without Type 1 reactions, as measured by qPCR. Moreover, we observed that keratinocytes but not macrophages up-regulated hBD2 and hBD3 in response to M. leprae stimulation in vitro. Corticosteroid treatment of patients with T1Rs caused a suppression of hBD2 and hBD3 in skin biopsies, as measured by qPCR. In vitro, corticosteroids suppressed M. leprae-dependent induction of hBD2 and hBD3 in keratinocytes. CONCLUSIONS:This study demonstrates that hBD3 is induced in leprosy Type 1 Reactions and suppressed by corticosteroids. Furthermore, our findings demonstrate that keratinocytes are responsive to M. leprae and lend support for additional studies on keratinocyte innate immunity in leprosy and T1Rs. TRIAL REGISTRATION:Controlled-Trials.com ISRCTN31894035. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 6 11 e1869 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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language |
English |
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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 Anna L Cogen Stephen L Walker Chrissy H Roberts Deanna A Hagge Kapil D Neupane Saraswoti Khadge Diana N J Lockwood Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Leprosy, a chronic granulomatous disease affecting the skin and nerves, is caused by Mycobacterium leprae (M. leprae). The type of leprosy developed depends upon the host immune response. Type 1 reactions (T1Rs), that complicate borderline and lepromatous leprosy, are due to an increase in cell-mediated immunity and manifest as nerve damage and skin inflammation. Owing to the increase in inflammation in the skin of patients with T1Rs, we sought to investigate the activation of the innate immune system during reactionary events. Specifically, we investigated the expression levels of human beta-defensins (hBDs) 2 and 3 in the skin of patients with T1Rs, in keratinocytes, and in macrophages stimulated with M. leprae and corticosteroids. RESULTS:Skin biopsies from twenty-three patients with Type 1 reactions were found to have higher transcript levels of hBD3 as compared to fifteen leprosy patients without Type 1 reactions, as measured by qPCR. Moreover, we observed that keratinocytes but not macrophages up-regulated hBD2 and hBD3 in response to M. leprae stimulation in vitro. Corticosteroid treatment of patients with T1Rs caused a suppression of hBD2 and hBD3 in skin biopsies, as measured by qPCR. In vitro, corticosteroids suppressed M. leprae-dependent induction of hBD2 and hBD3 in keratinocytes. CONCLUSIONS:This study demonstrates that hBD3 is induced in leprosy Type 1 Reactions and suppressed by corticosteroids. Furthermore, our findings demonstrate that keratinocytes are responsive to M. leprae and lend support for additional studies on keratinocyte innate immunity in leprosy and T1Rs. TRIAL REGISTRATION:Controlled-Trials.com ISRCTN31894035. |
format |
Article in Journal/Newspaper |
author |
Anna L Cogen Stephen L Walker Chrissy H Roberts Deanna A Hagge Kapil D Neupane Saraswoti Khadge Diana N J Lockwood |
author_facet |
Anna L Cogen Stephen L Walker Chrissy H Roberts Deanna A Hagge Kapil D Neupane Saraswoti Khadge Diana N J Lockwood |
author_sort |
Anna L Cogen |
title |
Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
title_short |
Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
title_full |
Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
title_fullStr |
Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
title_full_unstemmed |
Human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
title_sort |
human beta-defensin 3 is up-regulated in cutaneous leprosy type 1 reactions. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001869 https://doaj.org/article/e2a50e6795644c7bb418591eb87bb2c6 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 11, p e1869 (2012) |
op_relation |
http://europepmc.org/articles/PMC3486878?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0001869 https://doaj.org/article/e2a50e6795644c7bb418591eb87bb2c6 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001869 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
6 |
container_issue |
11 |
container_start_page |
e1869 |
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