Filaria-induced monocyte dysfunction and its reversal following treatment
Filaria-induced monocyte dysfunction and its reversal following treatment
复制标题
DOI：
10.1128/iai.01106-05
复制
发表时间：
2006-08-01
影响因子：
3.1
通讯作者：
Nutman, Thomas B.
中科院分区：
文献类型：
--
作者：
Semnani, Roshanak Tolouei;Keiser, Paul B.;Nutman, Thomas B.
丝虫感染中的单核细胞功能障碍被认为是淋巴丝虫病患者抗原特异性T细胞反应减弱的机制之一。在治疗前和治疗后8个月，评估了未受刺激和金黄色葡萄球菌科万I型细菌加γ干扰素刺激的丝虫感染患者和未感染健康供体单核细胞中细胞因子/趋化因子的产生和基因表达。从丝虫感染的个人的单核细胞与细胞内微丝蚴抗原镶嵌。此外，与来自未感染供体的单核细胞相比，来自这些个体的单核细胞产生白细胞介素-8（IL-8）、Exodus II、MIP-1 α、MIP-1 β和IL-1 α的能力较低，并且优先表达参与凋亡和粘附的基因。单剂量伊维菌素-阿苯达唑治疗8个月后，这些缺陷中的一些被逆转，单核细胞产生IL-8、IL-1 α、MIP-1 α和IL-10与未感染对照组相当。此外，与预处理表达相比，与蛋白质代谢相关的基因，特别是热休克蛋白的mRNA表达显著增加。这些数据表明，丝虫感染患者单核细胞的功能和基因表达发生了改变，但这种功能障碍在抗丝虫治疗后是部分可逆的。
Monocyte dysfunction in filarial infection has been proposed as one mechanism underlying the diminished antigen-specific T-cell response seen in patent lymphatic filariasis. Cytokine/chemokine production and gene expression in monocytes from fillaria-infected patients and uninfected healthy donors were assessed unstimulated and in response to stimulation with Staphylococcus aureus Cowan I bacteria plus gamma interferon both before and 8 months following treatment. Monocytes from filaria-infected individuals were studded with intracellular microfilarial antigens. Furthermore, monocytes from these individuals were less capable of producing interleukin-8 (IL-8), Exodus II, MIP-1 alpha, MIP-1 beta, and IL-1 alpha and preferentially expressed genes involved in apoptosis and adhesion compared with monocytes from uninfected donors. Eight months following treatment with a single dose of ivermectin-albendazole, some of these defects were reversed, with monocyte production of IL-8, IL-1 alpha, MIP-1 alpha, and IL-10 being comparable to that seen in the uninfected controls. In addition, a marked increase in mRNA expression of genes associated with protein metabolism, particularly heat shock proteins, was seen compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria-infected patients are altered but that this dysfunction is partially reversible following antifilarial treatment.