Suppressed Type 1, Type 2, and Type 17 Cytokine Responses in Active Tuberculosis in Children
Suppressed Type 1, Type 2, and Type 17 Cytokine Responses in Active Tuberculosis in Children
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DOI：
10.1128/cvi.05366-11
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发表时间：
2011-11-01
影响因子：
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通讯作者：
Babu, Subash
中科院分区：
文献类型：
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作者：
Kumar, N. Pavan;Anuradha, R.;Babu, Subash
已知1型细胞因子反应在儿童结核病（TB）免疫中起重要作用，尽管对其他可能重要的因素知之甚少。此外，儿童比成人更容易出现肺外结核表现。为了确定在控制感染和肺外播散中重要的免疫应答，我们检测了肺结核（PTB）和肺外结核（ETB）儿童的分枝杆菌特异性细胞因子应答，并将其与健康对照儿童（HC）进行比较。在PTB和ETB儿童之间，无论是无刺激还是分枝杆菌抗原（Ag）刺激后，细胞因子反应均无显著差异。另一方面，与HC相比，患有活动性TB的儿童在没有刺激和对分枝杆菌抗原有反应的情况下，1型（γ干扰素[IFN-γ]和肿瘤坏死因子α [TNF-α]）、2型（白细胞介素4 [IL-4]和IL-13）和17型（IL-17 A、IL-21和IL-23）相关细胞因子的产生显著减少。这与IL-10或转化生长因子β（TGF-β）产生的显着改变无关。在ETB儿童中，神经系统受累的儿童表现出更显着减少Ag驱动的IFN-γ和IL-17的产生。儿童结核病的特点是减少1型，2型和17型细胞因子的反应，与最深刻的减少有利于发展的神经系统结核病，这表明这些细胞因子在预防儿童结核病的关键作用。
Type 1 cytokine responses are known to play an important role in immunity to tuberculosis (TB) in children, although little is known about other factors that might be important. In addition, children are more prone to developing extrapulmonary manifestations of TB than adults. To identify the immune responses important both in control of infection and in extrapulmonary dissemination, we examined mycobacterium-specific cytokine responses of children with pulmonary TB (PTB) and extrapulmonary TB (ETB) and compared them with those of healthy control children (HC). No significant differences were found in the cytokine responses either with no stimulation or following mycobacterial-antigen (Ag) stimulation between children with PTB and ETB. On the other hand, children with active TB compared with HC showed markedly diminished production of type 1 (gamma interferon [IFN-gamma] and tumor necrosis factor alpha [TNF-alpha]), 2 (interleukin 4 [IL-4] and IL-13), and 17 (IL-17A, IL-21, and IL-23)-associated cytokines with no stimulation and in response to mycobacterial antigens. This was not associated with significantly altered production of IL-10 or transforming growth factor beta (TGF-beta). Among children with ETB, those with neurologic involvement exhibited more significantly diminished Ag-driven IFN-gamma and IL-17 production. Pediatric TB is characterized by diminished type 1, 2, and 17 cytokine responses, with the most profound diminution favoring development of neurologic TB, suggesting a crucial role for these cytokines in protection against pediatric tuberculosis.