IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis.,PLoS Pathogens

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IL-22 produced by type 3 innate lymphoid cells (ILC3s) reduces the mortality of type 2 diabetes mellitus (T2DM) mice infected with Mycobacterium tuberculosis.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2019-12-06 , DOI: 10.1371/journal.ppat.1008140
Deepak Tripathi ₁ , Rajesh Kumar Radhakrishnan ₁ , Ramya Sivangala Thandi ₁ , Padmaja Paidipally ₁ , Kamakshi Prudhula Devalraju ₂ , Venkata Sanjeev Kumar Neela ₂ , Madeline Kay McAllister ₁ , Buka Samten ₁ , Vijaya Lakshmi Valluri ₂ , Ramakrishna Vankayalapati ₁

Affiliation

Previously, we found that pathological immune responses enhance the mortality rate of Mycobacterium tuberculosis (Mtb)-infected mice with type 2 diabetes mellitus (T2DM). In the current study, we evaluated the role of the cytokine IL-22 (known to play a protective role in bacterial infections) and type 3 innate lymphoid cells (ILC3s) in regulating inflammation and mortality in Mtb-infected T2DM mice. IL-22 levels were significantly lower in Mtb-infected T2DM mice than in nondiabetic Mtb-infected mice. Similarly, serum IL-22 levels were significantly lower in tuberculosis (TB) patients with T2DM than in TB patients without T2DM. ILC3s were an important source of IL-22 in mice infected with Mtb, and recombinant IL-22 treatment or adoptive transfer of ILC3s prolonged the survival of Mtb-infected T2DM mice. Recombinant IL-22 treatment reduced serum insulin levels and improved lipid metabolism. Recombinant IL-22 treatment or ILC3 transfer prevented neutrophil accumulation near alveoli, inhibited neutrophil elastase 2 (ELA2) production and prevented epithelial cell damage, identifying a novel mechanism for IL-22 and ILC3-mediated inhibition of inflammation in T2DM mice infected with an intracellular pathogen. Our findings suggest that the IL-22 pathway may be a novel target for therapeutic intervention in T2DM patients with active TB disease.

中文翻译：

3 型先天淋巴细胞 (ILC3) 产生的 IL-22 可降低感染结核分枝杆菌的 2 型糖尿病 (T2DM) 小鼠的死亡率。

此前，我们发现病理性免疫反应会增加结核分枝杆菌（Mtb）感染的2型糖尿病（T2DM）小鼠的死亡率。在当前的研究中，我们评估了细胞因子 IL-22（已知在细菌感染中发挥保护作用）和 3 型先天淋巴细胞 (ILC3) 在调节 Mtb 感染的 T2DM 小鼠炎症和死亡率中的作用。感染 Mtb 的 T2DM 小鼠的 IL-22 水平显着低于未感染 Mtb 的小鼠。同样，患有 T2DM 的结核病 (TB) 患者的血清 IL-22 水平显着低于不患有 T2DM 的结核病患者。 ILC3是感染Mtb的小鼠中IL-22的重要来源，重组IL-22治疗或ILC3的过继转移可延长Mtb感染的T2DM小鼠的存活率。重组 IL-22 治疗可降低血清胰岛素水平并改善脂质代谢。重组IL-22治疗或ILC3转移可防止中性粒细胞在肺泡附近积聚，抑制中性粒细胞弹性蛋白酶2（ELA2）产生并防止上皮细胞损伤，从而确定了IL-22和ILC3介导的抑制细胞内炎症的T2DM小鼠炎症的新机制病原。我们的研究结果表明，IL-22 通路可能是患有活动性结核病的 T2DM 患者治疗干预的新靶点。

更新日期：2019-12-07

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