Nandakumar Vijayalakshmi, Hebrink Deanne, Jenson Paige, Kottom Theodore, Limper Andrew H
Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA.
Thoracic Diseases Research Unit, Department of Medicine, Mayo Clinic and Foundation, Rochester, Minnesota, USA
Infect Immun. 2017 Feb 23;85(3). doi: 10.1128/IAI.00939-16. Print 2017 Mar.
We explored differential polarization of macrophages during infection using a rat model of pneumonia. We observed enhanced pulmonary M1 macrophage polarization in immunosuppressed (IS) hosts, but an M2 predominant response in immunocompetent (IC) hosts following challenge. Increased inflammation and inducible nitric oxide synthase (iNOS) levels characterized the M1 response. However, macrophage ability to produce nitric oxide was defective. In contrast, the lungs of IC animals revealed a prominent M2 gene signature, and these macrophages effectively elicited an oxidative burst associated with clearance of In addition, during infection the expression of Dectin-1, a critical receptor for recognition and clearance of , was upregulated in macrophages of IC animals but suppressed in IS animals. In the absence of an appropriate cytokine milieu for M2 differentiation, induced an M1 response both and The M1 response induced by was plastic in nature and reversible with appropriate cytokine stimuli. Finally, we tested whether macrophage polarization can be modulated and used to help manage the pathogenesis of pneumonia by adoptive transfer. Treatment with both M1 and M2 cells significantly improved survival of -infected IS hosts. However, M2 treatment provided the best outcomes with efficient clearance of and reduced inflammation.
我们使用大鼠肺炎模型探究了感染过程中巨噬细胞的差异极化。我们观察到，免疫抑制（IS）宿主的肺部M1巨噬细胞极化增强，但免疫 competent（IC）宿主在受到攻击后呈现M2占主导的反应。炎症增加和诱导型一氧化氮合酶（iNOS）水平是M1反应的特征。然而，巨噬细胞产生一氧化氮的能力存在缺陷。相比之下，IC动物的肺部显示出显著的M2基因特征，并且这些巨噬细胞有效地引发了与清除相关的氧化爆发。此外，在感染期间，识别和清除的关键受体Dectin-1在IC动物的巨噬细胞中表达上调，但在IS动物中受到抑制。在缺乏适合M2分化的细胞因子环境时，在和中均诱导出M1反应。由诱导的M1反应本质上是可塑性的，并且在适当的细胞因子刺激下是可逆的。最后，我们测试了巨噬细胞极化是否可以被调节，并通过过继转移用于帮助控制肺炎的发病机制。用M1和M2细胞进行治疗均显著提高了感染的IS宿主的存活率。然而，M2治疗提供了最佳结果，具有高效清除和减轻炎症的效果。
