Fallert Beth A, Poveda Sandra, Schaefer Todd M, Pfeifer Melanie E, Sanghavi Sonali K, Watkins Simon C, Murphey-Corb Michael A, Tarwater Patrick M, Kirschner Denise E, Reinhart Todd A
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):16-26. doi: 10.1097/QAI.0b013e31815cea8b.
Lymphoid tissues are sites of soluble and cell-associated antigen sampling of peripheral tissues, and they are key compartments for the generation of cellular and humoral immune responses. Hilar lymph nodes (HiLNs), which drain the lungs, were examined to understand the effects of simian immunodeficiency virus (SIV) infection on this compartment of the immune system. Histologic and messenger RNA (mRNA) expression profiling approaches were used to determine the numbers, types, and distributions of SIV viral RNA cells and to identify differentially expressed genes in HiLNs during SIV infection. SIV RNA cells were found to be primarily CD68 and localized to paracortical and medullary regions early in infection, whereas they resided mainly in paracortex during AIDS. As SIV infection progressed, CXCL9, CXCL10, interferon-gamma, and Toll-like receptor 3 levels all increased. In contrast, CCL19 increased early in infection but decreased during AIDS, whereas CCL21 decreased progressively throughout infection. Finally, local levels of cellular activation were increased throughout infection. Taken together, these findings indicate that SIV infection leads to an inflammatory environment in lung-draining lymph nodes that is characterized by type 1 cytokines and chemokines and likely has an impact on the nature and strength of immune responses to pulmonary pathogens.
淋巴组织是外周组织可溶性和细胞相关抗原采样的场所,也是细胞免疫和体液免疫反应产生的关键区域。为了解猴免疫缺陷病毒(SIV)感染对免疫系统这一区域的影响,对引流肺部的肺门淋巴结(HiLNs)进行了检查。采用组织学和信使核糖核酸(mRNA)表达谱分析方法,确定SIV病毒RNA细胞的数量、类型和分布,并识别SIV感染期间HiLNs中差异表达的基因。发现SIV RNA细胞主要为CD68阳性,感染早期定位于副皮质区和髓质区,而在艾滋病期主要位于副皮质区。随着SIV感染的进展,CXCL9、CXCL10、干扰素-γ和Toll样受体3水平均升高。相比之下,CCL19在感染早期升高,但在艾滋病期降低,而CCL21在整个感染过程中逐渐降低。最后,整个感染过程中细胞活化的局部水平均升高。综上所述,这些发现表明SIV感染导致引流肺部的淋巴结出现以1型细胞因子和趋化因子为特征的炎症环境,可能对肺部病原体免疫反应的性质和强度产生影响。