I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Protozoa Immunology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
Science. 2024 Apr 5;384(6691):eabo7027. doi: 10.1126/science.abo7027.
Macrophages are functionally heterogeneous cells essential for apoptotic cell clearance. Apoptotic cells are defined by homogeneous characteristics, ignoring their original cell lineage identity. We found that in an interleukin-4 (IL-4)-enriched environment, the sensing of apoptotic neutrophils by macrophages triggered their tissue remodeling signature. Engulfment of apoptotic hepatocytes promoted a tolerogenic phenotype, whereas phagocytosis of T cells had little effect on IL-4-induced gene expression. In a mouse model of parasite-induced pathology, the transfer of macrophages conditioned with IL-4 and apoptotic neutrophils promoted parasitic egg clearance. Knockout of phagocytic receptors required for the uptake of apoptotic neutrophils and partially T cells, but not hepatocytes, exacerbated helminth infection. These findings suggest that the identity of apoptotic cells may contribute to the development of distinct IL-4-driven immune programs in macrophages.
巨噬细胞是功能异质性细胞，对于清除凋亡细胞至关重要。凋亡细胞的定义具有同质性特征，忽略了其原始细胞谱系身份。我们发现，在白细胞介素 4（IL-4）丰富的环境中，巨噬细胞对凋亡中性粒细胞的感应触发了它们的组织重塑特征。吞噬凋亡的肝细胞促进了耐受表型，而吞噬 T 细胞对 IL-4 诱导的基因表达几乎没有影响。在寄生虫诱导的病理模型的小鼠中，用 IL-4 和凋亡中性粒细胞条件化的巨噬细胞的转移促进了寄生虫卵的清除。吞噬凋亡中性粒细胞和部分 T 细胞所需的吞噬受体的敲除，而非肝细胞的敲除，加重了寄生虫感染。这些发现表明，凋亡细胞的身份可能有助于巨噬细胞中不同的 IL-4 驱动的免疫程序的发展。
