Institute of Experimental Hematology.
REBIRTH, Research Center for Translational and Regenerative Medicine.
Blood Adv. 2021 Dec 14;5(23):5190-5201. doi: 10.1182/bloodadvances.2021004853.
Primary or secondary immunodeficiencies are characterized by disruption of cellular and humoral immunity. Respiratory infections are a major cause of morbidity and mortality among immunodeficient or immunocompromised patients, with Staphylococcus aureus being a common offending organism. We propose here an adoptive macrophage transfer approach aiming to enhance impaired pulmonary immunity against S aureus. Our studies, using human-induced pluripotent stem cell-derived macrophages (iMφs), demonstrate efficient antimicrobial potential against methicillin-sensitive and methicillin-resistant clinical isolates of S aureus. Using an S aureus airway infection model in immunodeficient mice, we demonstrate that the adoptive transfer of iMφs is able to reduce the bacterial load more than 10-fold within 20 hours. This effect was associated with reduced granulocyte infiltration and less damage in lung tissue of transplanted animals. Whole transcriptome analysis of iMφs compared with monocyte-derived macrophages indicates a more profound upregulation of inflammatory genes early after infection and faster normalization 24 hours postinfection. Our data demonstrate high therapeutic efficacy of iMφ-based immunotherapy against S aureus infections and offer an alternative treatment strategy for immunodeficient or immunocompromised patients.
原发性或继发性免疫缺陷症的特征是细胞和体液免疫的破坏。呼吸道感染是免疫缺陷或免疫抑制患者发病和死亡的主要原因，金黄色葡萄球菌是常见的致病病原体。在这里，我们提出了一种过继性巨噬细胞转移方法，旨在增强针对金黄色葡萄球菌的受损肺部免疫。我们的研究使用人诱导多能干细胞衍生的巨噬细胞（iMφs），证明了对耐甲氧西林敏感和耐甲氧西林金黄色葡萄球菌临床分离株具有有效的抗菌潜力。在免疫缺陷小鼠的金黄色葡萄球菌气道感染模型中，我们证明了 iMφs 的过继转移能够在 20 小时内将细菌负荷降低 10 倍以上。这种效果与移植动物肺部的粒细胞浸润减少和损伤减少有关。与单核细胞衍生的巨噬细胞相比，iMφs 的全转录组分析表明，感染后早期炎症基因的上调更为明显，感染后 24 小时更快恢复正常。我们的数据证明了基于 iMφ 的免疫疗法治疗金黄色葡萄球菌感染的高治疗效果，并为免疫缺陷或免疫抑制患者提供了一种替代治疗策略。
