Medina Freddy A, Cohen Alex W, de Almeida Cecilia J, Nagajyothi Fnu, Braunstein Vicki L, Teixeira Mauro Martins, Tanowitz Herbert B, Lisanti Michael P
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Microbes Infect. 2007 Mar;9(3):325-33. doi: 10.1016/j.micinf.2006.12.011. Epub 2007 Jan 9.
In recent years, host cell caveolae/caveolins have emerged as potentially important targets for pathogenic microorganisms; therefore, we investigated the role of caveolin-1 (Cav-1) in T. cruzi infection using Cav-1 null mice. Cav-1 null and wild type mice were infected with the virulent Tulahuen strain. The mortality was 100% in both groups, but death was slightly delayed in wild type mice. The parasitemia in the Cav-1 null mice was significantly reduced compared with wild type littermates. Histopathologic examination of the heart revealed numerous pseudocysts, myonecrosis, and marked inflammation, which was similar in both mouse groups. Real-time PCR confirmed these observations. Infection of cultured cardiac fibroblasts obtained from Cav-1 null and wild type mice revealed no differences in infectivity. Determination of serum levels of several inflammatory mediators revealed a striking reduction in IFN-gamma, TNF-alpha and components of the nitric oxide pathway in infected Cav-1 null mice. Infection of wild type mice resulted in the expected enhancement of inflammatory mediators. The defective production of chemokines and cytokines observed in vivo is in part attributed to Cav-1 null macrophages. Despite these marked differences in the response to infection by inflammatory mediators between the two mouse strains, the final outcome was similar. These results suggest that Cav-1 may play an important role in the normal development of immune responses.
近年来，宿主细胞小窝/小窝蛋白已成为致病微生物潜在的重要靶点；因此，我们使用小窝蛋白-1（Cav-1）基因敲除小鼠研究了Cav-1在克氏锥虫感染中的作用。将Cav-1基因敲除小鼠和野生型小鼠感染强毒株图拉洪株。两组小鼠的死亡率均为100%，但野生型小鼠的死亡略有延迟。与野生型同窝小鼠相比，Cav-1基因敲除小鼠的寄生虫血症显著降低。心脏组织病理学检查显示两组小鼠均有大量假囊肿、心肌坏死和明显炎症。实时定量PCR证实了这些观察结果。对从Cav-1基因敲除小鼠和野生型小鼠获得的培养心脏成纤维细胞进行感染，结果显示感染性无差异。对几种炎症介质的血清水平进行测定发现，感染的Cav-1基因敲除小鼠的干扰素-γ、肿瘤坏死因子-α和一氧化氮途径的成分显著降低。野生型小鼠感染后炎症介质出现预期的增加。体内观察到的趋化因子和细胞因子产生缺陷部分归因于Cav-1基因敲除巨噬细胞。尽管两种小鼠品系在对感染的炎症介质反应方面存在这些显著差异，但最终结果相似。这些结果表明，Cav-1可能在免疫反应的正常发展中起重要作用。
