Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA 02114, USA.
J Infect Dis. 2011 Nov;204(9):1349-57. doi: 10.1093/infdis/jir544. Epub 2011 Sep 7.
Recent studies demonstrate that long palate, lung, and nasal epithelium clone 1 protein (LPLUNC1) is involved in immune responses to Vibrio cholerae, and that variations in the LPLUNC1 promoter influence susceptibility to severe cholera in humans. However, no functional role for LPLUNC1 has been identified.
We investigated the role of LPLUNC1 in immune responses to V. cholerae, assessing its affect on bacterial growth and killing and on innate inflammatory responses to bacterial outer membrane components, including purified lipopolysaccharide (LPS) and outer membrane vesicles. We performed immunostaining for LPLUNC1 in duodenal biopsies from cholera patients and uninfected controls.
LPLUNC1 decreased proinflammatory innate immune responses to V. cholerae and Escherichia coli LPS. The effect of LPLUNC1 was dose-dependent and occurred in a TLR4-dependent manner. LPLUNC1 did not affect lipoprotein-mediated TLR2 activation. Immunostaining demonstrated expression of LPLUNC1 in Paneth cells in cholera patients and controls.
Our results demonstrate that LPLUNC1 is expressed in Paneth cells and likely plays a role in modulating host inflammatory responses to V. cholerae infection. Attenuation of innate immune responses to LPS by LPLUNC1 may have implications for the maintenance of immune homeostasis in the intestine.
最近的研究表明，长腭、肺和鼻上皮克隆 1 蛋白（LPLUNC1）参与了对霍乱弧菌的免疫反应，LPLUNC1 启动子的变异影响了人类对严重霍乱的易感性。然而，尚未确定 LPLUNC1 的功能作用。
我们研究了 LPLUNC1 在对霍乱弧菌免疫反应中的作用，评估了它对细菌生长和杀伤的影响，以及对细菌外膜成分（包括纯化的脂多糖[LPS]和外膜囊泡）固有炎症反应的影响。我们对霍乱患者和未感染对照者的十二指肠活检进行了 LPLUNC1 免疫染色。
LPLUNC1 降低了对霍乱弧菌和大肠杆菌 LPS 的促炎固有免疫反应。LPLUNC1 的作用呈剂量依赖性，并以 TLR4 依赖性方式发生。LPLUNC1 不影响脂蛋白介导的 TLR2 激活。免疫染色显示 LPLUNC1 在霍乱患者和对照者的潘氏细胞中表达。
我们的结果表明，LPLUNC1 在潘氏细胞中表达，可能在调节宿主对霍乱弧菌感染的炎症反应中发挥作用。LPLUNC1 对 LPS 的固有免疫反应的抑制作用可能对维持肠道免疫稳态具有重要意义。
