All-trans retinoic acid in combination with primaquine clears pneumocystis infection.
All-trans retinoic acid in combination with primaquine clears pneumocystis infection.
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DOI：
10.1371/journal.pone.0053479
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lee CH
中科院分区：
文献类型：
--
作者：
Lei GS;Zhang C;Shao S;Jung HW;Durant PJ;Lee CH
肺孢子虫肺炎（PcP）发生于免疫功能低下的患者。肺泡巨噬细胞在识别、吞噬和降解肺孢子虫中起关键作用，但其数量在PcP中减少。我们对PcP过程中各种炎症成分的研究发现，髓源性抑制细胞（MDSC）在肺孢子虫肺炎（PcP）小鼠和大鼠的肺中积累。我们假设，全反式维甲酸（ATRA），维生素A的代谢产物，治疗可以有效地控制肺孢子虫（Pc）感染诱导MDSC分化为AM。在PcP的啮齿动物模型中，我们发现5周的ATRA治疗减少了肺中MDSC的数量，并增加了清除Pc感染的AM的数量。我们还发现，ATRA与伯氨喹联合治疗PcP与甲氧苄啶和磺胺甲恶唑联合治疗PcP一样有效，并在两周内完全消除肺中的MDSC和Pc微生物。全反式维甲酸-伯氨喹联合治疗3周后未见PcP复发。通过该方案还实现了PC感染动物的延长存活。这是第一次成功开发出一种将免疫调节剂与抗生素相结合的PcP治疗方案，使宿主能够有效地防御感染。我们的研究结果可以作为一个模型，为其他感染MDSC积累的新疗法的发展。
Pneumocystis pneumonia (PcP) develops in immunocompromised patients. Alveolar macrophages play a key role in the recognition, phagocytosis, and degradation of Pneumocystis, but their number is decreased in PcP. Our study of various inflammatory components during PcP found that myeloid-derived suppressor cells (MDSCs) accumulate in the lungs of mice and rats with Pneumocystis pneumonia (PcP). We hypothesized that treatment with all-trans retinoic acid (ATRA), a metabolite of vitamin A, may effectively control Pneumocystis (Pc) infection by inducing MDSCs to differentiate to AMs. In rodent models of PcP, we found that 5 weeks of ATRA treatment reduced the number of MDSCs in the lungs and increased the number of AMs which cleared Pc infection. We also found that ATRA in combination with primaquine was as effective as the combination of trimethoprim and sulfamethaxazole for treatment of PcP and completely eliminated MDSCs and Pc organisms in the lungs in two weeks. No relapse of PcP was seen after three weeks of the ATRA-primaquine combination treatment. Prolonged survival of Pc-infected animals was also achieved by this regimen. This is the very first successful development of a therapeutic regimen for PcP that combines an immune modulator with an antibiotic, enabling the hosts to effectively defend the infection. Results of our study may serve as a model for development of novel therapies for other infections with MDSC accumulation.
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影响因子：
120.7
作者：
Kovacs, Joseph A.;Masur, Henry
通讯作者：
Masur, Henry
影响因子：
8.8
作者：
Martin, S. I.;Fishman, J. A.
通讯作者：
Fishman, J. A.
DOI：
10.4049/jimmunol.0901864
发表时间：
2010-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bhagwat SP;Wright TW;Gigliotti F
通讯作者：
Gigliotti F
影响因子：
3.1
作者：
Lasbury, ME;Lin, P;Lee, CH
通讯作者：
Lee, CH
影响因子：
45.3
作者：
LEE, JS;NEWMAN, RA;HONG, WK
通讯作者：
HONG, WK