Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice.
Visceral leishmaniasis (VL) is a chronic and fatal disease in humans and dogs caused by the intracellular protozoan parasites, Leishmania donovani and L. infantum (L. chagasi). Relapse of disease is frequent in immunocompromised patients, in which the number of VL cases has been increasing recently....
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ftdoajarticles:oai:doaj.org/article:7ef5c2c303c843caaf29bf0829e99d03 2023-05-15T15:15:27+02:00 Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. Saruda Tiwananthagorn Kazuya Iwabuchi Manabu Ato Tatsuya Sakurai Hirotomo Kato Ken Katakura 2012-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0001798 https://doaj.org/article/7ef5c2c303c843caaf29bf0829e99d03 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3424244?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 doi:10.1371/journal.pntd.0001798 1935-2727 1935-2735 https://doaj.org/article/7ef5c2c303c843caaf29bf0829e99d03 PLoS Neglected Tropical Diseases, Vol 6, Iss 8, p e1798 (2012) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2012 ftdoajarticles https://doi.org/10.1371/journal.pntd.0001798 2022-12-31T09:24:05Z Visceral leishmaniasis (VL) is a chronic and fatal disease in humans and dogs caused by the intracellular protozoan parasites, Leishmania donovani and L. infantum (L. chagasi). Relapse of disease is frequent in immunocompromised patients, in which the number of VL cases has been increasing recently. The present study is aimed to improve the understanding of mechanisms of L. donovani persistence in immunocompromised conditions using alymphoplastic aly/aly mice. Hepatic parasite burden, granuloma formation and induction of regulatory T cells were determined for up to 7 months after the intravenous inoculation with L. donovani promastigotes. While control aly/+ mice showed a peak of hepatic parasite growth at 4 weeks post infection (WPI) and resolved the infection by 8 WPI, aly/aly mice showed a similar peak in hepatic parasite burden but maintained persistent in the chronic phase of infection, which was associated with delayed and impaired granuloma maturation. Although hepatic CD4(+)Foxp3(+) but not CD8(+)Foxp3(+) T cells were first detected at 4 WPI in both strains of mice, the number of CD4(+)Foxp3(+) T cells was significantly increased in aly/aly mice from 8 WPI. Immunohistochemical analysis demonstrated the presence of Foxp3(+) T cells in L. donovani-induced hepatic granulomas and perivascular neo-lymphoid aggregates. Quantitative real-time PCR analysis of mature granulomas collected by laser microdissection revealed the correlation of Foxp3 and IL-10 mRNA level. Furthermore, treatment of infected aly/aly mice with anti-CD25 or anti-FR4 mAb resulted in significant reductions in both hepatic Foxp3(+) cells and parasite burden. Thus, we provide the first evidence that CD4(+)Foxp3(+) Tregs mediate L. donovani persistence in the liver during VL in immunodeficient murine model, a result that will help to establish new strategies of immunotherapy against this intracellular protozoan pathogen. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Aly ENVELOPE(132.394,132.394,68.420,68.420) PLoS Neglected Tropical Diseases 6 8 e1798 |
institution |
Open Polar |
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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 Saruda Tiwananthagorn Kazuya Iwabuchi Manabu Ato Tatsuya Sakurai Hirotomo Kato Ken Katakura Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Visceral leishmaniasis (VL) is a chronic and fatal disease in humans and dogs caused by the intracellular protozoan parasites, Leishmania donovani and L. infantum (L. chagasi). Relapse of disease is frequent in immunocompromised patients, in which the number of VL cases has been increasing recently. The present study is aimed to improve the understanding of mechanisms of L. donovani persistence in immunocompromised conditions using alymphoplastic aly/aly mice. Hepatic parasite burden, granuloma formation and induction of regulatory T cells were determined for up to 7 months after the intravenous inoculation with L. donovani promastigotes. While control aly/+ mice showed a peak of hepatic parasite growth at 4 weeks post infection (WPI) and resolved the infection by 8 WPI, aly/aly mice showed a similar peak in hepatic parasite burden but maintained persistent in the chronic phase of infection, which was associated with delayed and impaired granuloma maturation. Although hepatic CD4(+)Foxp3(+) but not CD8(+)Foxp3(+) T cells were first detected at 4 WPI in both strains of mice, the number of CD4(+)Foxp3(+) T cells was significantly increased in aly/aly mice from 8 WPI. Immunohistochemical analysis demonstrated the presence of Foxp3(+) T cells in L. donovani-induced hepatic granulomas and perivascular neo-lymphoid aggregates. Quantitative real-time PCR analysis of mature granulomas collected by laser microdissection revealed the correlation of Foxp3 and IL-10 mRNA level. Furthermore, treatment of infected aly/aly mice with anti-CD25 or anti-FR4 mAb resulted in significant reductions in both hepatic Foxp3(+) cells and parasite burden. Thus, we provide the first evidence that CD4(+)Foxp3(+) Tregs mediate L. donovani persistence in the liver during VL in immunodeficient murine model, a result that will help to establish new strategies of immunotherapy against this intracellular protozoan pathogen. |
format |
Article in Journal/Newspaper |
author |
Saruda Tiwananthagorn Kazuya Iwabuchi Manabu Ato Tatsuya Sakurai Hirotomo Kato Ken Katakura |
author_facet |
Saruda Tiwananthagorn Kazuya Iwabuchi Manabu Ato Tatsuya Sakurai Hirotomo Kato Ken Katakura |
author_sort |
Saruda Tiwananthagorn |
title |
Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. |
title_short |
Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. |
title_full |
Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. |
title_fullStr |
Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. |
title_full_unstemmed |
Involvement of CD4⁺ Foxp3⁺ regulatory T cells in persistence of Leishmania donovani in the liver of alymphoplastic aly/aly mice. |
title_sort |
involvement of cd4⁺ foxp3⁺ regulatory t cells in persistence of leishmania donovani in the liver of alymphoplastic aly/aly mice. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doi.org/10.1371/journal.pntd.0001798 https://doaj.org/article/7ef5c2c303c843caaf29bf0829e99d03 |
long_lat |
ENVELOPE(132.394,132.394,68.420,68.420) |
geographic |
Arctic Aly |
geographic_facet |
Arctic Aly |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 6, Iss 8, p e1798 (2012) |
op_relation |
http://europepmc.org/articles/PMC3424244?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 doi:10.1371/journal.pntd.0001798 1935-2727 1935-2735 https://doaj.org/article/7ef5c2c303c843caaf29bf0829e99d03 |
op_doi |
https://doi.org/10.1371/journal.pntd.0001798 |
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PLoS Neglected Tropical Diseases |
container_volume |
6 |
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8 |
container_start_page |
e1798 |
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