絕大多數(shù)肺結(jié)核是由結(jié)核分枝桿菌引發(fā)的，這種細(xì)菌通過(guò)阻斷自然的免疫觸發(fā)反應(yīng)導(dǎo)致疾病的傳染,，而自然的免疫反應(yīng)一旦發(fā)生,，被感染的細(xì)胞就會(huì)死亡,。新研究工作日前在線(xiàn)發(fā)表在《自然—免疫學(xué)》期刊上,，為研制預(yù)防結(jié)核分枝桿菌疾病的新藥開(kāi)辟了一種可能的新途徑。
結(jié)核分枝桿菌能感染一種名為巨噬細(xì)胞的免疫細(xì)胞,，讓它們成為臨時(shí)性的細(xì)菌增生“孵化器”,，增生的細(xì)菌被釋放出來(lái)并去感染其他細(xì)胞。通常情況下,，被感染的巨噬細(xì)胞會(huì)經(jīng)歷一種名為細(xì)胞凋亡的死亡過(guò)程并觸發(fā)一種免疫反應(yīng),。
Heinz Remold和同事發(fā)現(xiàn)，結(jié)構(gòu)分枝菌阻止了巨噬細(xì)胞進(jìn)入凋亡過(guò)程,，但會(huì)通過(guò)一種名為“壞死”的方式讓巨噬細(xì)胞死亡,，這種細(xì)胞死亡的另一種方式讓細(xì)菌得以逃脫宿主細(xì)胞并感染新細(xì)胞。
通過(guò)揭示結(jié)核分枝細(xì)胞逃離免疫系統(tǒng)的方式,，新研究讓人們更加深入地認(rèn)識(shí)到結(jié)核病的發(fā)展過(guò)程,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Immunology，doi:10.1038/ni.1654,，Huixian Gan,，Heinz G Remold
Mycobacterium tuberculosis blocks crosslinking of annexin-1 and apoptotic envelope formation on infected macrophages to maintain virulence
Huixian Gan1, Jinhee Lee2, Fucheng Ren2, Minjian Chen1, Hardy Kornfeld2 & Heinz G Remold1
Abstract
Macrophages infected with attenuated Mycobacterium tuberculosis strain H37Ra become apoptotic, which limits bacterial replication and facilitates antigen presentation. Here we demonstrate that cells infected with H37Ra became apoptotic after the formation of an apoptotic envelope on their surface was complete. This process required exposure of phosphatidylserine on the cell surface, followed by deposition of the phospholipid-binding protein annexin-1 and then transglutaminase-mediated crosslinking of annexin-1 through its amino-terminal domain. In macrophages infected with the virulent strain H37Rv, in contrast, the amino-terminal domain of annexin-1 was removed by proteolysis, thus preventing completion of the apoptotic envelope, which resulted in macrophage death by necrosis. Virulent M. tuberculosis therefore avoids the host defense system by blocking formation of the apoptotic envelope, which leads to macrophage necrosis and dissemination of infection in the lung.
1 Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA.
2 Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
