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Involvement of CD4+ Foxp3+ Regulatory T Cells in Persistence of Leishmania donovani in the Liver of Alymphoplastic aly/aly Mice

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Title: Involvement of CD4+ Foxp3+ Regulatory T Cells in Persistence of Leishmania donovani in the Liver of Alymphoplastic aly/aly Mice
Authors: Tiwananthagorn, Saruda Browse this author
Iwabuchi, Kazuya Browse this author →KAKEN DB
Ato, Manabu Browse this author
Sakurai, Tatsuya Browse this author
Kato, Hirotomo Browse this author →KAKEN DB
Katakura, Ken Browse this author →KAKEN DB
Issue Date: 21-Aug-2012
Publisher: Public Library of Science
Journal Title: PLoS Neglected Tropical Diseases
Volume: 6
Issue: 8
Start Page: e1798
Publisher DOI: 10.1371/journal.pntd.0001798
Abstract: 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.
Type: article
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 片倉 賢

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