Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198.
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198
J Immunol. 2021 Feb 15;206(4):751-765. doi: 10.4049/jimmunol.2001042. Epub 2021 Jan 8.
Neurosurgery for brain tumor resection or epilepsy treatment requires a craniotomy to gain access to the brain. Despite prophylactic measures, infectious complications occur at a frequency of 1-3%, with approximately half caused by () that forms a biofilm on the bone flap and is recalcitrant to antibiotics. Using single-cell RNA sequencing in a mouse model of craniotomy infection, this study revealed the complex transcriptional heterogeneity of resident microglia and infiltrating monocytes in the brain, in addition to transcriptionally diverse granulocyte subsets in the s.c. galea and bone flap. In the brain, trajectory analysis identified the transition of microglia from a homeostatic/anti-inflammatory to proinflammatory and proliferative populations, whereas granulocytes in the brain demonstrated a trajectory from a granulocyte myeloid-derived suppressor cell (MDSC)-like phenotype to a small population of mature polymorphonuclear neutrophils (PMNs). In the galea, trajectory analysis identified the progression from two distinct granulocyte-MDSC-like populations to PMN clusters enriched for IFN signaling and cell cycle genes. Based on their abundance in the galea and bone flap, PMNs and MDSCs were depleted using anti-Ly6G, which resulted in increased bacterial burden. This revealed a critical role for PMNs in containment because MDSCs were found to attenuate PMN antibacterial activity, which may explain, in part, why craniotomy infection persists in the presence of PMN infiltrates. These results demonstrate the existence of a transcriptionally diverse leukocyte response that likely influences the chronicity of craniotomy infection.
神经外科切除脑肿瘤或治疗癫痫需要进行开颅手术以进入大脑。尽管采取了预防措施，但感染并发症的频率仍为 1-3%，其中约一半是由（）引起的，它在骨瓣上形成生物膜，并且对抗生素有抗性。本研究使用单细胞 RNA 测序在开颅感染的小鼠模型中，揭示了驻留小胶质细胞和浸润单核细胞在大脑中的复杂转录异质性，以及在 s.c. 帽状腱膜和骨瓣中的转录多样化粒细胞亚群。在大脑中，轨迹分析确定了小胶质细胞从稳态/抗炎到促炎和增殖群体的转变，而大脑中的粒细胞表现出从粒细胞髓系来源抑制细胞（MDSC）样表型到一小部分成熟多形核粒细胞（PMN）的轨迹。在帽状腱膜中，轨迹分析确定了从两个不同的粒细胞-MDSC 样群体到富含 IFN 信号和细胞周期基因的 PMN 簇的进展。基于它们在帽状腱膜和骨瓣中的丰度，使用抗 Ly6G 耗竭 PMN 和 MDSC，这导致细菌负荷增加。这揭示了 PMN 在（）控制中的关键作用，因为 MDSC 被发现减弱了 PMN 的抗菌活性，这部分解释了为什么在存在 PMN 浸润的情况下开颅感染仍然持续存在。这些结果表明存在转录多样化的白细胞反应，这可能影响开颅感染的慢性化。
