Chopra V, Fadl A A, Sha J, Chopra S, Galindo C L, Chopra A K
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas 77555-1070, USA.
J Toxicol Environ Health A. 2006 Jul;69(14):1345-70. doi: 10.1080/15287390500361792.
Host immune mechanisms were proposed to decline under microgravity conditions during spaceflights, which might result in severe infections in astronauts. Therefore, it was important to investigate the effects of microgravity on infecting organisms and their interaction with host cells. Data showed that simulated microgravity (SMG) conditions markedly increased production of the enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin, which induced fluid secretory responses in a mouse model. SMG also enhanced production of tumor necrosis factor-alpha in murine macrophages infected with enteropathogenic E. coli (EPEC). In a similar fashion, simulated microgravity conditions augmented the invasive potential of Salmonella enterica serovar typhimurium and enhanced production of tumor necrosis-factor alpha in S. typhimurium-infected epithelial cells. Furthermore, coculturing of macrophages and S. typhimurium in a simulated microgravity environment resulted in activation of stress-associated mitogen-activated protein kinase kinase 4. Using the antiorthostatic tail suspension mouse model, which simulates some aspects of microgravity, oral inoculation of S. typhimurium markedly reduced the 50% lethal dose compared to mice infected under normal gravitational conditions. Microarray analysis revealed simulated microgravity-induced alterations in the expression of 22 genes in S. typhimurium, and protein expression profiles were altered in both EPEC and S. typhimurium, based on two-dimensional gel electrophoresis. These studies indicated alterations in the virulence potential of bacteria and in host responses to these pathogens under simulated microgravity conditions, which may represent an important environmental signal. Such studies are essential for better understanding bacterial-host cell interactions, particularly in the context of spaceflights and space habitations of long duration.
有观点认为，在太空飞行的微重力条件下，宿主免疫机制会衰退，这可能导致宇航员发生严重感染。因此，研究微重力对感染性生物体及其与宿主细胞相互作用的影响非常重要。数据显示，模拟微重力（SMG）条件显著增加了产肠毒素大肠杆菌（ETEC）热敏肠毒素的产生，该毒素在小鼠模型中可诱导液体分泌反应。模拟微重力还增强了感染肠致病性大肠杆菌（EPEC）的小鼠巨噬细胞中肿瘤坏死因子-α的产生。同样，模拟微重力条件增强了鼠伤寒沙门氏菌的侵袭潜力，并增加了感染鼠伤寒沙门氏菌的上皮细胞中肿瘤坏死因子-α的产生。此外，在模拟微重力环境中巨噬细胞与鼠伤寒沙门氏菌共培养导致应激相关的丝裂原活化蛋白激酶激酶4激活。使用模拟微重力某些方面的抗重力尾悬吊小鼠模型，与在正常重力条件下感染的小鼠相比，口服接种鼠伤寒沙门氏菌显著降低了50%致死剂量。微阵列分析显示模拟微重力诱导鼠伤寒沙门氏菌中22个基因的表达发生改变，基于二维凝胶电泳，EPEC和鼠伤寒沙门氏菌中的蛋白质表达谱均发生改变。这些研究表明，在模拟微重力条件下，细菌的毒力潜力以及宿主对这些病原体的反应发生了改变，这可能代表一种重要的环境信号。此类研究对于更好地理解细菌与宿主细胞的相互作用至关重要，尤其是在长期太空飞行和太空居住的背景下。
