Attenuated Nephritis in Inducible Nitric Oxide Synthase Knockout C57BL/6 Mice and Pulmonary Hemorrhage in CB17 SCID and Recombination Activating Gene 1 Knockout C57BL/6 Mice Infected with Leptospira interrogans
Attenuated Nephritis in Inducible Nitric Oxide Synthase Knockout C57BL/6 Mice and Pulmonary Hemorrhage in CB17 SCID and Recombination Activating Gene 1 Knockout C57BL/6 Mice Infected with Leptospira interrogans
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DOI：
10.1128/iai.05099-11
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发表时间：
2011-07-01
影响因子：
3.1
通讯作者：
Athanazio, Daniel A.
中科院分区：
文献类型：
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作者：
Bandeira, Mauricio;Santos, Cleiton S.;Athanazio, Daniel A.
本研究的目的是研究不能产生功能性B淋巴细胞和T淋巴细胞的小鼠肺出血（PH）的频率，并探讨诱导型一氧化氮合酶基因（Inos）敲除（KO）对体内间质性肾炎的频率和严重程度的影响。我们研究了传染性钩端螺旋体哥本哈根毒株毒株感染的结果。实验动物为Inos KO小鼠、重组激活基因1 (Rag1) KO小鼠、CB17严重联合免疫缺陷（SCID）小鼠以及野生型（WT） C57BL/6和BALB/c对照。Inos KO和WT小鼠存活，无钩端螺旋体病临床症状。Inos - KO小鼠肾炎发生频率和严重程度明显降低。所有Rag1 KO和SCID小鼠死于急性钩端螺旋体病，而所有WT小鼠存活。分别接种10(7)和10(6)钩端螺旋体，在57%和94%的Rag1 KO小鼠和83%和100%的SCID小鼠中观察到PH。在WT对照组中没有PH的证据。总之，Inos基因的缺失对钩端螺旋体感染的影响可以忽略不计，尽管我们观察到这组患者对间质性肾炎的易感性降低。值得注意的是，功能性b细胞和t细胞淋巴细胞的缺失并不能排除PH的发生。这些数据提供了证据，表明钩端螺旋体病的PH可能不仅仅与自身免疫机制有关。
The aims of this study were to investigate the frequency of pulmonary hemorrhage (PH) in mice unable to produce functional B and T lymphocytes and to explore the effect of an inducible nitric oxide synthase gene (Inos) knockout (KO) on the frequency/severity of interstitial nephritis in vivo. We studied the outcome of infection by the virulent Leptospira interrogans serovar Copenhageni strain Cop. The animals used were Inos KO mice, recombination activating gene 1 (Rag1) KO mice, CB17 severe combined immunodeficiency (SCID) mice, and the respective wild-type (WT) C57BL/6 and BALB/c controls. The Inos KO and WT mice survived with no clinical symptoms of leptospirosis. The frequency and severity of nephritis was significantly lower in the Inos KO mice. All of the Rag1 KO and SCID animals died of acute leptospirosis, whereas all of the WT mice survived. PH was observed in 57 and 94% of Rag1 KO mice and in 83 and 100% of SCID mice, using inoculum doses of 10(7) and 10(6) leptospires, respectively. There was no evidence of PH in the WT controls. In conclusion, the loss of the Inos gene had a negligible effect on the outcome of leptospiral infection, although we observed a reduced susceptibility for interstitial nephritis in this group. Of note, the absence of functional B-and T-cell lymphocytes did not preclude the occurrence of PH. These data provide evidence that PH in leptospirosis may not be related only to autoimmune mechanisms.