A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection
A potential role for indoleamine 2,3-dioxygenase (IDO) in Rhodococcus equi infection
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DOI：
10.1016/j.vetimm.2010.07.013
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发表时间：
2010-12-01
影响因子：
1.8
通讯作者：
Watson, J. L.
中科院分区：
文献类型：
--
作者：
Heller, M. C.;Drew, C. P.;Watson, J. L.
马红球菌（Rhodococcus equi）是一种兼性胞内致病菌，可感染宿主巨噬细胞和树突状细胞（DC）并在其中增殖。马红球菌感染的马单核细胞来源的DC和肺泡巨噬细胞对色氨酸的需求量增加，色氨酸代谢途径中的起始酶吲哚胺2 3-双加氧酶（IDO）表达上调。equi的细胞外和细胞内生长进行了评估。在马肺泡巨噬细胞中，INDO对R Nut的细胞内增殖没有影响。马感染IDO（-/-）（B6，129-（Indotm 1Alm）/J）（n = 22）和菌株匹配对照（C57 BL/6 J）（n = 20）小鼠通过腹膜内注射马立克次体感染3和6天。两组之间肝或脾中的细菌计数没有差异。伽马（IFN γ）肿瘤坏死因子-α（TNF α）IL-4 IL-6 IL-10 IL-12 IL-23叉头框P3（FoxP 3）和转化生长因子-β感染后第6天，IDO（-/-）组肝组织炎症评分明显高于对照组（P= 0.05），感染后第3天肝组织TGF β表达明显低于对照组（P = 0.05）。与对照小鼠相比，在第3天（P= 0.02）和第6天（P= 0.03），FOXP 3的免疫染色显示IDO（-/-）小鼠肝脏中FOXP 3+调节性T细胞的数量较低。小鼠相应地在该组织中FOXP 3和TGF β的表达较低，并且FOXP 3 +调节性T细胞我们的结论是，激活的巨噬细胞和DC的IDO表达在抑制对R的炎症反应中发挥作用。马感染小鼠（C）2010爱思唯尔B V保留所有权利
Rhodococcus equi is a facultative intracellular bacterial pathogen of foals and immunocompromised humans that infects and proliferates within host macrophages and dendritic cells (DC) Indoleamine 2 3-dioxygenase (IDO) the initial enzyme in the tryptophan catabolism pathway is upregulated in R equi infected equine monocyte-derived DC and alveolar macrophages Tryptophan requirement of R. equi for extracellular and intracellular growth was assessed Growth of R. equi in minimal media did not require tryptophan and pharmacologic inhibition of IDO had no effect on intracellular proliferation of R Nut in equine alveolar macrophages To investigate an immune-regulatory role for INDO in R. equi infection IDO(-/-) (B6, 129-(Indotm1Alm) /J) (n = 22) and strain matched control (C57BL/6J) (n = 20) mice were infected with R equi by intraperitoneal injection for 3 and 6 days There was no difference in bacterial counts in liver or spleen between the two groups Histological sections of liver and spleen were assigned inflammation scores and RT-PCR for Interferon-gamma (IFN gamma) tumor necrosis factor-alpha (TNF alpha) IL-4 IL-6 IL-10 IL-12 IL-23 forkhead box P3 (FoxP3) and transforming growth factor-beta (TGF beta) was performed on liver and spleen Liver tissue of IDO(-/-) had higher inflammation scores at 6 days post-infection (PI) (P=0 05) and had decreased expression of TGF beta at 3 days PI (P=0 01) and FOXP3 at 3 days (P=0 02) and 6 days (P=0 03) compared to control mice Immunostaining for FOXP3 showed lower numbers of FOXP3+ regulatory T cells in liver of IDO(-/-) mice 6 days PI Prolonged inflammation in the liver tissue of IDO(-/-) mice corresponded with lower expression of FOXP3 and TGF beta in that tissue and also with lower numbers of FOXP3+ regulatory T cells We conclude that IDO expression by activated macrophages and DC plays a role in dampening the inflammatory response to R. equi infection in mice (C) 2010 Elsevier B V All rights reserved