Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
Bacillus Calmette-Guerin vaccine-mediated neuroprotection is associated with regulatory T-cell induction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.
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DOI：
10.1002/jnr.23253
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发表时间：
2013-10
影响因子：
4.2
通讯作者：
Kaufman DL
中科院分区：
文献类型：
--
作者：
Laćan G;Dang H;Middleton B;Horwitz MA;Tian J;Melega WP;Kaufman DL
We previously showed that, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD), vaccination with bacillus Calmette-Guerin (BCG) prior to MPTP exposure limited the loss of striatal dopamine (DA) and dopamine transporter (DAT) and prevented the activation of nigral microglia. Here, we conducted BCG dose studies and investigated the mechanisms underlying BCG vaccination’s neuroprotective effects in this model. We found that a dose of 1 × 106 cfu BCG led to higher levels of striatal DA and DAT ligand binding (28% and 42%, respectively) in BCG-vaccinated vs. unvaccinated MPTP-treated mice, but without a significant increase in substantia nigra tyrosine hydroxylase-staining neurons. Previous studies showed that BCG can induce regulatory T cells (Tregs) and that Tregs are neuroprotective in models of neurodegenerative diseases. However, MPTP is lymphotoxic, so it was unclear whether Tregs were maintained after MPTP treatment and whether a relationship existed between Tregs and the preservation of striatal DA system integrity. We found that, 21 days post-MPTP treatment, Treg levels in mice that had received BCG prior to MPTP were threefold greater than those in MPTP-only-treated mice and elevated above those in saline-only-treated mice, suggesting that the persistent BCG infection continually promoted Treg responses. Notably, the magnitude of the Treg response correlated positively with both striatal DA levels and DAT ligand binding. Therefore, BCG vaccine-mediated neuroprotection is associated with Treg levels in this mouse model. Our results suggest that BCG-induced Tregs could provide a new adjunctive therapeutic approach to ameliorating pathology associated with PD and other neurodegenerative diseases.
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影响因子：
14.8
作者：
Jackson-Lewis, Vernice;Przedborski, Serge
通讯作者：
Przedborski, Serge
DOI：
10.1093/brain/awr074
发表时间：
2011-05
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Beers DR;Henkel JS;Zhao W;Wang J;Huang A;Wen S;Liao B;Appel SH
通讯作者：
Appel SH
影响因子：
11.1
作者：
Henkel, Jenny S.;Beers, David R.;Wen, Shixiang;Rivera, Andreana L.;Toennis, Karen M.;Appel, Joan E.;Zhao, Weihua;Moore, Dan H.;Powell, Suzanne Z.;Appel, Stanley H.
通讯作者：
Appel, Stanley H.
DOI：
10.1073/pnas.0400569101
发表时间：
2004-06-22
影响因子：
11.1
作者：
Benner, EJ;Mosley, RL;Gendelman, HE
通讯作者：
Gendelman, HE
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.