M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes.
M-CSF Mediates Host Defense during Bacterial Pneumonia by Promoting the Survival of Lung and Liver Mononuclear Phagocytes.
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DOI：
10.4049/jimmunol.1600306
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发表时间：
2016-06-15
期刊：
影响因子：
--
通讯作者：
Mehrad B
中科院分区：
文献类型：
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作者：
Bettina A;Zhang Z;Michels K;Cagnina RE;Vincent IS;Burdick MD;Kadl A;Mehrad B
革兰氏阴性细菌性肺炎是一种常见和危险的感染，由于病原菌对抗生素的耐药性不断增加，治疗选择越来越少。单核吞噬细胞系统是由组织内巨噬细胞、树突状细胞和单核细胞衍生细胞组成的异质性白细胞群，它们在抵抗肺炎中起着至关重要的作用，但在感染期间调节其维持和功能的机制尚不清楚。巨噬细胞集落刺激因子（M-CSF）对单核吞噬细胞有多种作用，但其在肺炎中的作用尚不清楚。因此，我们在小鼠感染模型中验证了M-CSF在细菌性肺炎期间单核吞噬细胞介导的宿主防御中所必需的假设。M-CSF基因缺失或免疫中和导致存活降低、细菌负担增加和肺损伤加重。M-CSF对于感染期间肺单核吞噬细胞的扩张是必需的，但不影响骨髓或血液单核细胞的数量、前体的增殖或白细胞向肺的募集。相反，M-CSF对肺炎期间肺和肝单核吞噬细胞的存活和抗微生物功能至关重要，缺乏M-CSF会导致细菌传播到肝脏和肝坏死。我们得出结论，M-CSF通过介导肺和肝中单核吞噬细胞的存活和抗微生物功能，对宿主防御细菌性肺炎至关重要。
Gram-negative bacterial pneumonia is a common and dangerous infection with diminishing treatment options due to increasing antibiotic resistance among causal pathogens. The mononuclear phagocyte system is a heterogeneous group of leukocytes composed of tissue-resident macrophages, dendritic cells and monocyte-derived cells that are critical in defense against pneumonia, but mechanisms that regulate their maintenance and function during infection are poorly defined. Macrophage-colony stimulating factor (M-CSF) has myriad effects on mononuclear phagocytes but its role in pneumonia is unknown. We therefore tested the hypothesis that M-CSF is required for mononuclear phagocyte-mediated host defenses during bacterial pneumonia in a murine model of infection. Genetic deletion or immunoneutralization of M-CSF resulted in reduced survival, increased bacterial burden and greater lung injury. M-CSF was necessary for the expansion of lung mononuclear phagocytes during infection but did not affect the number of bone marrow or blood monocytes, the proliferation of precursors or the recruitment of leukocytes to the lungs. In contrast, M-CSF was essential to survival and anti-microbial functions of both lung and liver mononuclear phagocytes during pneumonia and its absence resulted in bacterial dissemination to the liver and hepatic necrosis. We conclude that M-CSF is critical to host defenses against bacterial pneumonia by mediating survival and anti-microbial functions of mononuclear phagocytes in the lungs and liver.