Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7
Innate Killing of Leishmania donovani by Macrophages of the Splenic Marginal Zone Requires IRF-7
复制标题
脾边缘区巨噬细胞对杜氏利什曼原虫的先天杀伤需要 IRF-7
作者：
Rebecca A. Phillips;M. Svensson;Naveed Aziz;A. Maroof;Najmeeyah Brown;Lynette Beattie;N. Signoret;P. Kaye
高度吞噬的巨噬细胞排列在脾的边缘区（MZ）和淋巴结被膜下窦。虽然这些巨噬细胞具有多种功能，包括吸收和清除血液和淋巴传播的病原体，但对它们在病原体吸收后采用的效应机制知之甚少。在这里，我们结合了基因表达谱和RNAi使用的基质巨噬细胞系与在野生型和基因靶向小鼠的边缘区巨噬细胞（MZM）和边缘嗜金属巨噬细胞（MMM）的杀利什曼活性的原位分析。我们的数据表明，干扰素调节因子-7（IRF-7）在调节这些专门的脾巨噬细胞亚群对细胞内杜氏利什曼原虫的杀伤中起着关键作用。因此，本研究确定了IRF-7作为先天杀微生物活性的调节剂对这种和其他非病毒细胞内病原体的新作用。这项研究还强调了在研究病原体与这种功能多样的细胞谱系相互作用时选择适当的巨噬细胞群体的重要性。
Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ after pathogen uptake. Here, we have combined gene expression profiling and RNAi using a stromal macrophage cell line with in situ analysis of the leishmanicidal activity of marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM) in wild type and gene targeted mice. Our data demonstrate a critical role for interferon regulatory factor-7 (IRF-7) in regulating the killing of intracellular Leishmania donovani by these specialised splenic macrophage sub-populations. This study, therefore, identifies a new role for IRF-7 as a regulator of innate microbicidal activity against this, and perhaps other, non-viral intracellular pathogens. This study also highlights the importance of selecting appropriate macrophage populations when studying pathogen interactions with this functionally diverse lineage of cells.