Down-modulation of lung immune responses by interleukin-10 and transforming growth factor β (TGF-β) and analysis of TGF-β receptors I and II in active tuberculosis
Down-modulation of lung immune responses by interleukin-10 and transforming growth factor β (TGF-β) and analysis of TGF-β receptors I and II in active tuberculosis
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DOI：
10.1128/iai.72.5.2628-2634.2004
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发表时间：
2004-05-01
影响因子：
3.1
通讯作者：
Silva, JRLE
中科院分区：
文献类型：
--
作者：
Bonecini-Almeida, MG;Ho, JL;Silva, JRLE
影响进展为活动性结核病（TB）的免疫因素仍然定义不清。在这项研究中，我们研究了免疫调节细胞因子和受体的表达，通过使用肺结核患者，其他肺部疾病患者（OLD患者）和健康志愿者（VOL）获得的肺支气管肺泡灌洗液细胞，通过使用逆转录酶PCR，转化生长因子β（TGF-β）生物活性测定，和酶免疫测定。TB患者比OLD患者更可能共表达TGF-β受体I（RI）和RII mRNA，以及白细胞介素-10（IL-10）mRNA（从而表明采集时肺泡细胞中基因转录的活性状态）。与此相反，γ干扰素（IFN-γ）和IL-2的mRNA被视为在结核病和老年患者。同样，与OLD患者和Vol患者相比，TB患者肺内IL-10、IFN-γ和生物活性TGF-β的稳态蛋白水平显著升高。这些数据表明，免疫抑制剂IL-10和TGF-β的联合产生，以及TGF-β RI和RII的共表达，（对TGF-β的细胞应答所需的），可能起下调宿主抗结核分枝杆菌免疫的作用，从而允许不受控制的细菌复制和明显的疾病。阐明了M.结核病触发的这些免疫元件的表达可能提供结核病免疫发病机制的分子水平的理解。
Immune factors influencing progression to active tuberculosis (TB) remain poorly defined. In this study, we investigated the expression of immunoregulatory cytokines and receptors by using lung bronchoalveolar lavage cells obtained from patients with pulmonary TB, patients with other lung diseases (OLD patients), and healthy volunteers (VOL) by using reverse transcriptase PCR, a transforming growth factor beta (TGF-beta) bioactivity assay, and an enzyme immunoassay. TB patients were significantly more likely than OLD patients to coexpress TGF-beta receptor I (RI) and RII mRNA, as well as interleukin-10 (IL-10) mRNA (thereby indicating the state of active gene transcription in the alveolar cells at harvest). In contrast, gamma interferon (IFN-gamma) and IL-2 mRNA was seen in both TB and OLD patients. Likewise, significantly elevated pulmonary steady-state protein levels of IL-10, IFN-gamma, and bioactive TGF-beta were found in TB patients versus those in OLD patients and VOL. These data suggest that the combined production of the immunosuppressants IL-10 and TGF-beta, as well as coexpression of TGF-beta RI and RII (required for cellular response to TGF-beta), may act to down-modulate host anti-Mycobacterium tuberculosis immunity and thereby allow uncontrolled bacterial replication and overt disease. Delineating the underlying mechanisms of M. tuberculosis-triggered expression of these immune elements may provide a molecular-level understanding of TB immunopathogenesis.