Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Center, Tyler.
Bhagwan Mahavir Medical Research Centre, Hyderabad, India.
J Infect Dis. 2018 Mar 28;217(8):1323-1333. doi: 10.1093/infdis/jiy034.
In the current study, we determined the effects of interleukin (IL)-21 on human natural killer (NK) cells and monocyte responses during Mycobacterium tuberculosis (Mtb) infection.
We found that Mtb stimulated CD4+ and NK T cells from healthy individuals with latent tuberculosis infection (LTBI+) are major sources of IL-21. CD4+ cells from tuberculosis patients secreted less IL-21 than did CD4+ cells from healthy LTBI+ individuals. Interleukin-21 had no direct effect on Mtb-stimulated monocytes.
Interleukin-21-activated NK cells produced interferon (IFN)-γ, perforin, granzyme B, and granulysin; lysed Mtb-infected monocytes; and reduced Mtb growth. Interleukin-21-activated NK cells also enhanced IL-1β, IL-18, and CCL4/macrophage-inflammatory protein (MIP)-1β production and reduced IL-10 production by Mtb-stimulated monocytes. Recombinant IL-21 (1) inhibited Mtb growth, (2) enhanced IFN-γ, IL-1β, IL-18, and MIP-1β, and (3) reduced IL-10 expression in the lungs of Mtb-infected Rag2 knockout mice.
These findings suggest that activated T cells enhance NK cell responses to lyse Mtb-infected human monocytes and restrict Mtb growth in monocytes through IL-21 production. Interleukin-21-activated NK cells also enhance the immune response by augmenting IL-1β, IL-18, and MIP-1β production and reducing IL-10 production by monocytes in response to an intracellular pathogen.
在本研究中，我们确定了白细胞介素（IL）-21 对人类自然杀伤（NK）细胞和单核细胞对结核分枝杆菌（Mtb）感染反应的影响。
我们发现，Mtb 刺激潜伏性结核感染（LTBI+）的健康个体中的 CD4+和 NK T 细胞是 IL-21 的主要来源。与健康 LTBI+个体的 CD4+细胞相比，结核病患者的 CD4+细胞分泌的 IL-21 较少。IL-21 对 Mtb 刺激的单核细胞没有直接作用。
IL-21 激活的 NK 细胞产生干扰素（IFN）-γ、穿孔素、颗粒酶 B 和颗粒酶；裂解 Mtb 感染的单核细胞；并减少 Mtb 生长。IL-21 激活的 NK 细胞还增强了 Mtb 刺激的单核细胞中 IL-1β、IL-18 和 CCL4/巨噬细胞炎症蛋白（MIP）-1β的产生，并减少了 Mtb 刺激的单核细胞中 IL-10 的产生。重组 IL-21（1）抑制 Mtb 生长，（2）增强 IFN-γ、IL-1β、IL-18 和 MIP-1β，（3）降低 Mtb 感染 Rag2 基因敲除小鼠肺部的 IL-10 表达。
这些发现表明，活化的 T 细胞通过产生 IL-21 增强 NK 细胞对裂解 Mtb 感染的人类单核细胞的反应，并限制单核细胞中的 Mtb 生长。IL-21 激活的 NK 细胞还通过增强 IL-1β、IL-18 和 MIP-1β 的产生以及减少单核细胞对细胞内病原体的 IL-10 产生来增强免疫反应。
