Attenuation of Toll-Like Receptor Expression and Function in Latent Tuberculosis by Coexistent Filarial Infection with Restoration Following Antifilarial Chemotherapy
Attenuation of Toll-Like Receptor Expression and Function in Latent Tuberculosis by Coexistent Filarial Infection with Restoration Following Antifilarial Chemotherapy
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DOI：
10.1371/journal.pntd.0000489
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发表时间：
2009-07-01
影响因子：
3.8
通讯作者：
Nutman, Thomas B.
中科院分区：
文献类型：
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作者：
Babu, Subash;Bhat, Sajid Q.;Nutman, Thomas B.
结核分枝杆菌(Mtb)和丝虫混合感染非常普遍，丝虫感染的存在可能调节控制Mtb感染所需的Toll样受体(TLR)依赖的免疫反应。通过分析基线和分枝杆菌抗原刺激的TLR1、2、4和9的表达(在有或没有丝虫感染的潜伏性结核病患者中)，我们能够证明丝虫感染，与结核分枝杆菌感染一致，显著降低基线和结核分枝杆菌抗原特异性TLR2和TLR9的表达。此外，丝虫/结核混合感染者对TLR2和9配体的促炎细胞因子反应显著减少。淋巴丝虫病的明确治疗显著恢复了潜伏性结核病患者的促炎细胞因子反应。在潜伏期结核病中，丝虫感染对分枝杆菌特异性TLR介导的保护性免疫反应具有深远的抑制作用，提示了一种新的机制，即伴随丝虫感染易导致人类活动性结核病的发展。
Mycobacterium tuberculosis (Mtb) and filarial coinfection is highly prevalent, and the presence of filarial infections may regulate the Toll-like receptor (TLR)-dependent immune response needed to control Mtb infection. By analyzing the baseline and mycobacterial antigen-stimulated expression of TLR1, 2, 4, and 9 (in individuals with latent tuberculosis [TB] with or without filarial infection), we were able to demonstrate that filarial infection, coincident with Mtb, significantly diminishes both baseline and Mtb antigen-specific TLR2 and TLR9 expression. In addition, pro-inflammatory cytokine responses to TLR2 and 9 ligands are significantly diminished in filaria/TB-coinfected individuals. Definitive treatment of lymphatic filariasis significantly restores the pro-inflammatory cytokine responses in individuals with latent TB. Coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific TLR-mediated immune responses in latent tuberculosis and suggests a novel mechanism by which concomitant filarial infections predispose to the development of active tuberculosis in humans.