Up-Regulation of TLR2 and TLR4 in Dendritic Cells in Response to HIV Type 1 and Coinfection with Opportunistic Pathogens
Up-Regulation of TLR2 and TLR4 in Dendritic Cells in Response to HIV Type 1 and Coinfection with Opportunistic Pathogens
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DOI：
10.1089/aid.2010.0302
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发表时间：
2011-10-01
影响因子：
1.5
通讯作者：
Urcuqui-Inchima, Silvio
中科院分区：
文献类型：
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作者：
Hernandez, Juan C.;Arteaga, Jose;Urcuqui-Inchima, Silvio
引发针对与HIV-1感染相关的机会性病原体的先天免疫应答的能力是AIDS发病机制的一个重要方面。Toll样受体（TLR）在先天性免疫中起着重要作用，但在HIV-1合并机会性感染的患者中，TLR表达的调控尚未见报道。在这种情况下，我们已经评估了TLR 2和TLR 4的表达在单核细胞，浆细胞样树突状细胞，髓样树突状细胞的HIV-1患者或无机会性感染。根据病毒载量、高效抗逆转录病毒治疗（HAART）和是否存在机会性感染对49名HIV-1感染者进行分类，21名健康受试者作为对照。与无机会性感染的HIV-1患者和健康受试者相比，在合并机会性感染的HIV-1患者（无HAART）的髓样树突状细胞中观察到TLR 2和TLR 4表达增加，而在浆细胞样树突状细胞中观察到TLR 4表达增加。此外，TLR 2的表达较高的机会性感染的患者没有HAART和上调TLR的表达在HIV-1合并感染的机会性感染的患者更明显的树突状细胞来源于结核分枝杆菌合并感染的个人。结果表明，TLR的表达在先天免疫细胞上调的患者与高HIV-1载量和共感染机会病原体。我们认为，调节TLRs的表达代表了一种机制，促进HIV-1复制和艾滋病的发病机制，在合并感染机会致病菌的患者。
The ability to trigger an innate immune response against opportunistic pathogens associated with HIV-1 infection is an important aspect of AIDS pathogenesis. Toll-like receptors (TLRs) play a critical role in innate immunity against pathogens, but in HIV-1 patients coinfected with opportunistic infections, the regulation of TLR expression has not been studied. In this context, we have evaluated the expression of TLR2 and TLR4 in monocytes, plasmacytoid dendritic cells, and myeloid dendritic cells of HIV-1 patients with or without opportunistic infections. Forty-nine HIV-1-infected individuals were classified according to viral load, highly active antiretroviral therapy (HAART), and the presence or absence of opportunistic infections, and 21 healthy subjects served as controls. Increased expression of TLR2 and TLR4 was observed in myeloid dendritic cells of HIV-1 patients coinfected with opportunistic infections (without HAART), while TLR4 increased in plasmacytoid dendritic cells, compared to both HIV-1 without opportunistic infections and healthy subjects. Moreover, TLR2 expression was higher in patients with opportunistic infections without HAART and up-regulation of TLR expression in HIV-1 patients coinfected with opportunistic infections was more pronounced in dendritic cells derived from individuals coinfected with Mycobacterium tuberculosis. The results indicate that TLR expression in innate immune cells is up-regulated in patients with a high HIV-1 load and coinfected with opportunistic pathogens. We suggest that modulation of TLRs expression represents a mechanism that promotes HIV-1 replication and AIDS pathogenesis in patients coinfected with opportunistic pathogens.