Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella enterica serovar Typhimurium infection
Caveolin-1-deficient mice show defects in innate immunity and inflammatory immune response during Salmonella enterica serovar Typhimurium infection
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DOI：
10.1128/iai.00949-06
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发表时间：
2006-12-01
影响因子：
3.1
通讯作者：
Lisanti, Michael P.
中科院分区：
文献类型：
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作者：
Medina, Freddy A.;de Almeida, Cecilia J.;Lisanti, Michael P.
许多研究表明病原体与小窝有关。然而，到目前为止，还没有研究显示小窝蛋白-1在调节针对病原体的免疫应答中的作用。有趣的是，已显示小窝蛋白-1的表达在免疫细胞中响应于脂多糖（LPS）以受调节的方式发生。在这里，我们试图确定小窝蛋白-1（Cav-1）表达在沙门氏菌发病机制中的作用。Cav-1（-/-）小鼠在用沙门氏菌鼠伤寒血清型攻击时显示存活率显著降低。Cav-1（-/-）小鼠的脾脏和组织负荷显著较高。然而，Cav-1（-/-）巨噬细胞感染血清型鼠伤寒没有导致细菌入侵的差异。此外，Cav-1（-/-）小鼠显示炎性细胞因子、趋化因子和一氧化氮的产生增加。尽管如此，Cav-1（-/-）小鼠无法控制沙门氏菌的全身感染。Cav-1（-/-）小鼠中趋化因子产生的增加导致更多的嗜中性粒细胞浸润到肉芽肿中，但没有改变肉芽肿的数量。这伴随着肝脏坏死增加。然而，Cav-1（-/-）巨噬细胞显示增加炎症反应和增加一氧化氮的生产在体外响应沙门氏菌LPS。这些结果表明，小窝蛋白-1在调节巨噬细胞的抗炎反应中起关键作用。总之，这些数据表明，缺乏小窝蛋白-1的巨噬细胞产生毒性介质的增加可能是小窝蛋白-1缺乏小鼠对S.鼠伤寒沙门氏菌
A number of studies have shown an association of pathogens with caveolae. To this date, however, there are no studies showing a role for caveolin-1 in modulating immune responses against pathogens. Interestingly, expression of caveolin-1 has been shown to occur in a regulated manner in immune cells in response to lipopolysaccharide (LPS). Here, we sought to determine the role of caveolin-1 (Cav-1) expression in Salmonella pathogenesis. Cav-1(-/-) mice displayed a significant decrease in survival when challenged with Salmonella enterica serovar Typhimurium. Spleen and tissue burdens were significantly higher in Cav-1(-/-) mice. However, infection of Cav-1(-/-) macrophages with serovar Typhimurium did not result in differences in bacterial invasion. In addition, Cav-1(-/-) mice displayed increased production of inflammatory cytokines, chemokines, and nitric oxide. Regardless of this, Cav-1(-/-) mice were unable to control the systemic infection of Salmonella. The increased chemokine production in Cav-1(-/-) mice resulted in greater infiltration of neutrophills into granulomas but did not alter the number of granulomas present. This was accompanied by increased necrosis in the liver. However, Cav-1(-/-) macrophages displayed increased inflammatory responses and increased nitric oxide production in vitro in response to Salmonella LPS. These results show that caveolin-1 plays a key role in regulating anti-inflammatory responses in macrophages. Taken together, these data suggest that the increased production of toxic mediators from macrophages lacking caveolin-1 is likely to be responsible for the marked susceptibility of caveolin-I-deficient mice to S. enterica serovar Typhimurium.