HIV 感染者潜伏性和活动性结核病中 IL-17 和 IL-22 的产生。

IL-17 and IL-22 production in HIV+ individuals with latent and active tuberculosis.

机构信息

Immunology & Molecular Biology Department, Bhagwan Mahavir Medical Research Centre, A. C. Guards, Hyderabad, TS, 500004, India.

Clinical Division, Cheyutha, LEPRA Society, Cherlapally, Hyderabad, 501301, India.

出版信息

BMC Infect Dis. 2018 Jul 11;18(1):321. doi: 10.1186/s12879-018-3236-0.

BACKGROUND

IL-17 and IL-22 cytokines play an important role in protective immune responses against Mycobacterium tuberculosis (Mtb) infection. Information on the production of these cytokines and the factors that regulate their production in the context of human immunodeficiency virus (HIV) and latent tuberculosis infection (LTBI) or active tuberculosis disease (ATB) is limited. In the current study, we compared the production of these two cytokines by PBMC of HIV-LTBI+ and HIV + LTBI+ individuals in response to Mtb antigens CFP-10 (culture filtrate protein) and ESAT-6 (Early Secretory Antigenic Target). We also determined the mechanisms involved in their production.

METHODS

We cultured Peripheral Blood Mononuclear Cells (PBMCs) from HIV- individuals and HIV+ patients with latent tuberculosis and active disease with CFP-10 and ESAT-6. Production of IL-17, IL-22 and PD1 (Programmed Death 1), ICOS (Inducible T-cell Costimulator), IL-23R and FoxP3 (Forkhead box P3) expression on CD4+ T cells was measured.

RESULTS

In response to Mtb antigens CFP-10 and ESAT-6, freshly isolated PBMCs from HIV+ LTBI+ and HIV+ active TB patients produced less IL-17 and IL-22 and more IL-10, expressed less IL-23R, and more PD1 and expanded to more FoxP3+ cells. Active TB infection in HIV+ individuals further inhibited antigen specific IL-17 and IL-22 production compared to those with LTBI. Neutralization of PD1 restored IL-23R expression, IL-17 and IL-22 levels and lowered IL-10 production and reduced expansion of FoxP3 T cells.

CONCLUSIONS

In the current study we found that increased PD1 expression in HIV + LTBI+ and HIV+ active TB patients inhibits IL-17, IL-22 production and IL-23R expression in response to Mtb antigens CFP-10 and ESAT-6.

背景

白细胞介素 17（IL-17）和白细胞介素 22（IL-22）细胞因子在针对结核分枝杆菌（Mycobacterium tuberculosis，Mtb）感染的保护性免疫反应中发挥重要作用。关于这些细胞因子的产生以及在人类免疫缺陷病毒（human immunodeficiency virus，HIV）和潜伏性结核感染（latent tuberculosis infection，LTBI）或活动性结核疾病（active tuberculosis disease，ATB）背景下调节其产生的因素的信息有限。在目前的研究中，我们比较了 HIV-LTBI+和 HIV+LTBI+个体的外周血单核细胞（peripheral blood mononuclear cells，PBMC）在对 Mtb 抗原 CFP-10（培养滤液蛋白）和 ESAT-6（早期分泌抗原靶 6）产生这些两种细胞因子的情况。我们还确定了它们产生的机制。

方法

我们培养了 HIV 个体和潜伏性和活动性结核疾病的 HIV+患者的外周血单核细胞（peripheral blood mononuclear cells，PBMC），并用 CFP-10 和 ESAT-6 进行培养。测量了 CD4+T 细胞上 IL-17、IL-22 和 PD1（程序性死亡 1）、ICOS（诱导型 T 细胞共刺激因子）、IL-23R 和 FoxP3（叉头框 P3）的表达以及其产生的 IL-10。

结果

在对 Mtb 抗原 CFP-10 和 ESAT-6 的反应中，来自 HIV+LTBI+和 HIV+活动性结核患者的新鲜分离的 PBMC 产生较少的 IL-17 和 IL-22，而产生更多的 IL-10，表达较少的 IL-23R，产生更多的 PD1 和更多的 FoxP3+细胞。与 LTBI 患者相比，HIV+个体的活动性结核感染进一步抑制了抗原特异性的 IL-17 和 IL-22 的产生。PD1 的中和恢复了 IL-23R 的表达、IL-17 和 IL-22 水平，并降低了 IL-10 的产生和 FoxP3 T 细胞的扩增。