Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans
Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans
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DOI：
10.1099/jmm.0.46620-0
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发表时间：
2006-09-01
影响因子：
3
通讯作者：
Koyama, Hideki
中科院分区：
文献类型：
--
作者：
Aratani, Yasuaki;Kura, Fumiaki;Koyama, Hideki
中性粒细胞产生的活性氧对隐球菌感染的体内作用尚未得到广泛认可。髓过氧化物酶（MPO）是一种嗜中性的酶，其催化从H2 O2产生次卤酸如HOCl。本研究在MPO-/-小鼠模型中研究了MPO在新生隐球菌免疫防御中的作用。IMPO-/-小鼠鼻内或静脉内感染C. neoformans比相同攻击的野生型小鼠低。MPO-/-小鼠鼻内注射C.新生小鼠的肺真菌负荷显著大于野生型小鼠。在第7天，MPO-/-小鼠与野生型小鼠相比具有显著更高的白细胞介素（IL）-4的肺浓度和更低的IL-2、IL-12 p70和干扰素（IFN）-γ的浓度，表明IMPO-/-小鼠中对C.新人类在病理学上，鼻内感染的MPO-1-小鼠比野生型小鼠表现出更严重的肺炎，这与肺中IL-1 α/β水平的增加有关。此外，在MPO-/-小鼠中，肺部感染扩散到大脑，偶尔出现脑膜炎。感染MPO-/-小鼠脑内角质形成细胞因子（KC）水平明显高于对照组。鼻内和静脉内感染均导致MPO-/-小鼠脾脏中真菌数量高于野生型，表明对C.新生儿不仅在肺中，而且在没有MPO的情况下在脾中。总之，这些数据表明MPO在隐球菌感染的反应中起主要作用。
The in vivo contribution of reactive oxygen species produced by neutrophils against Cryptococcus infection is not widely recognized. Myeloperoxiclase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from H2O2. This study investigated the role of MPO in immunological defence against Cryptococcus neoformans in an MPO-cleficient (MPO-/-) mouse model. The survival of IMPO-/- mice infected either intranasally or intravenously with C. neoformans was lower than that of identically challenged wild-type mice. The MPO-/- mice that received intranasal injection of C. neoformans had significantly larger lung fungal burdens than wild-type mice. On day 7, MPO-/- mice had a significantly higher lung concentration of interleukin (IL)-4 and lower concentrations of IL-2, IL-12p70 and interferon (IFN)-gamma than wild-type mice, suggesting a weak Th1 response in the IMPO-/- mice to C. neoformans. Pathologically, the MPO-1- mice with intranasal infection showed more severe pneumonia than wild-type mice, which was associated with an increase in the levels of IL-1 alpha/beta in the lungs. In addition, in MPO-/- mice, the pulmonary infection disseminated to the brain with occasional meningitis. The keratinocyte-clerived cytolkine (KC) level in the brain of infected MPO-/- mice was higher than that of control mice. Both intranasal and intravenous infections resulted in a higher number of fungi in the spleen of MPO-/- mice compared to wild-type, suggesting decreased resistance to C. neoformans not only in the lungs but also in the spleen in the absence of MPO. Taken together, these data suggest a major role of MPO in the response to cryptococcal infection.