Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure.
Pneumocystis murina colonization in immunocompetent surfactant protein A deficient mice following environmental exposure.
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环境暴露后，小鼠肺孢子虫在免疫活性表面活性蛋白 A 缺陷小鼠中定植。
DOI：
10.1186/1465-9921-10-10
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发表时间：
2009-02-19
影响因子：
5.8
通讯作者：
Walzer PD
中科院分区：
文献类型：
--
作者：
Linke MJ;Ashbaugh AD;Demland JA;Walzer PD
肺囊虫是一种机会致病菌，可在免疫功能低下的人和动物中引起肺炎。肺囊虫定植在免疫正常的宿主中也被发现，并可能加重其他肺部疾病。表面活性蛋白A （SP-A）是一种天然宿主防御分子，在宿主对肺囊虫的反应中起作用。为分析SP-A对肺囊虫定殖的保护作用，采用逆转录酶定量PCR （qPCR）和酶联免疫吸附试验（ELISA）检测SP-A缺失免疫活性小鼠（KO）和野生型小鼠（WT）对肺囊虫定殖的易感性。在免疫正常的WT和KO小鼠中检测鼠腹假体特异性血清抗体，表明这两种小鼠都曾在动物设施内暴露于鼠腹假体。然而，P. murina mRNA仅在KO小鼠的肺中通过qPCR检测到。mRNA表达的发生率和水平在8-10周达到峰值，在16-18周下降到不可检测的水平。当小鼠免疫抑制时，也仅在KO小鼠中检测到鼠单胞菌囊肿。在暴露于KO小鼠的SCID小鼠中检测到P. murina mRNA，表明免疫正常的KO小鼠能够将感染传播给免疫缺陷小鼠。肺细胞反应似乎是清除定植的原因。免疫功能正常的KO小鼠肺中CD4+和CD8+ t细胞的回收比WT小鼠多，并且在CD4+细胞耗尽的KO小鼠中的定植未被清除。这些数据支持SP-A在保护具有免疫能力的宿主免受鼠腹假体定植方面的重要作用，并为研究人类环境暴露获得的肺囊虫定植提供了模型。结果还表明，即使在屏障条件下，也很难使小鼠不暴露于鼠腹假单胞菌。
Pneumocystis spp. are opportunistic pathogens that cause pneumonia in immunocompromised humans and animals. Pneumocystis colonization has also been detected in immunocompetent hosts and may exacerbate other pulmonary diseases. Surfactant protein A (SP-A) is an innate host defense molecule and plays a role in the host response to Pneumocystis. To analyze the role of SP-A in protecting the immunocompetent host from Pneumocystis colonization, the susceptibility of immunocompetent mice deficient in SP-A (KO) and wild-type (WT) mice to P. murina colonization was analyzed by reverse-transcriptase quantitative PCR (qPCR) and serum antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Detection of P. murina specific serum antibodies in immunocompetent WT and KO mice indicated that the both strains of mice had been exposed to P. murina within the animal facility. However, P. murina mRNA was only detected by qPCR in the lungs of the KO mice. The incidence and level of the mRNA expression peaked at 8–10 weeks and declined to undetectable levels by 16–18 weeks. When the mice were immunosuppressed, P. murina cyst forms were also only detected in KO mice. P. murina mRNA was detected in SCID mice that had been exposed to KO mice, demonstrating that the immunocompetent KO mice are capable of transmitting the infection to immunodeficient mice. The pulmonary cellular response appeared to be responsible for the clearance of the colonization. More CD4+ and CD8+ T-cells were recovered from the lungs of immunocompetent KO mice than from WT mice, and the colonization in KO mice depleted CD4+ cells was not cleared. These data support an important role for SP-A in protecting the immunocompetent host from P. murina colonization, and provide a model to study Pneumocystis colonization acquired via environmental exposure in humans. The results also illustrate the difficulties in keeping mice from exposure to P. murina even when housed under barrier conditions.
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DOI：
10.1007/s10096-004-1151-3
发表时间：
2004-07-01
影响因子：
4.5
作者：
Calderón, E;de la Horra, C;Varela, JM
通讯作者：
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影响因子：
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作者：
Beard, CB;Fox, MR;Colley, DG
通讯作者：
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影响因子：
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作者：
Beharka, AA;Gaynor, CD;Schlesinger, LS
通讯作者：
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影响因子：
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作者：
Davis, J. L.;Welsh, D. A.;Huang, L.
通讯作者：
Huang, L.
DOI：
10.1164/ajrccm.161.4.9906072
发表时间：
2000-04-01
影响因子：
24.7
作者：
Arozullah, AM;Yarnold, PR;Bennett, CL
通讯作者：
Bennett, CL