Sloan Erica K, Nguyen Christina T, Cox Benjamin F, Tarara Ross P, Capitanio John P, Cole Steve W
University of California Los Angeles, Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, CA, USA.
Brain Behav Immun. 2008 Feb;22(2):185-94. doi: 10.1016/j.bbi.2007.07.008. Epub 2007 Sep 17.
The sympathetic nervous system regulates immune responses in part through direct innervation of lymphoid organs. Recent data indicate that viral infections can alter the structure of lymph node innervation. To determine the molecular mechanisms underlying sympathetic denervation during Simian Immunodeficiency Virus (SIV) infection, we assessed the expression of neurotrophic factors and neuromodulatory cytokines within lymph nodes from experimentally infected rhesus macaques. Transcription of nerve growth factor (NGF), brain-derived neurotropic factor (BDNF) and neurotrophin-4 (NT4) decreased significantly in vivo during chronic SIV infection, whereas expression of the neuro-inhibitory cytokine interferon-gamma (IFN gamma) was up-regulated. Acute SIV infection of macaque leukocytes in vitro induced similar changes in the expression of neurotrophic and neuro-inhibitory factors, indicative of an innate immune response. Statistical mediation analyses of data from in vivo lymph node gene expression suggested that coordinated changes in expression of multiple neuromodulatory factors may contribute to SIV-induced depletion of catecholaminergic varicosities within lymphoid tissue. Given previous evidence that lymph node catecholaminergic varicosities can enhance SIV replication in vivo, these results are consistent with the hypothesis that reduced expression of neurotrophic factors during infection could constitute a neurobiological component of the innate immune response to viral infection.
交感神经系统部分通过对淋巴器官的直接神经支配来调节免疫反应。最近的数据表明，病毒感染可改变淋巴结神经支配的结构。为了确定猿猴免疫缺陷病毒（SIV）感染期间交感神经去神经支配的分子机制，我们评估了实验感染的恒河猴淋巴结内神经营养因子和神经调节细胞因子的表达。在慢性SIV感染期间，体内神经生长因子（NGF）、脑源性神经营养因子（BDNF）和神经营养因子-4（NT4）的转录显著下降，而神经抑制细胞因子γ干扰素（IFNγ）的表达上调。体外对猕猴白细胞进行急性SIV感染可诱导神经营养和神经抑制因子表达发生类似变化，这表明存在先天性免疫反应。对体内淋巴结基因表达数据进行的统计中介分析表明，多种神经调节因子表达的协同变化可能导致SIV诱导的淋巴组织内儿茶酚胺能曲张体减少。鉴于先前有证据表明淋巴结儿茶酚胺能曲张体可在体内增强SIV复制，这些结果与以下假设一致，即感染期间神经营养因子表达降低可能构成对病毒感染的先天性免疫反应的神经生物学组成部分。
