Mycobacterium avium Infection Induces H-Ferritin Expression in Mouse Primary Macrophages by Activating Toll-Like Receptor 2

Important for both host and pathogen survivals, iron is a key factor in determining the outcome of an infectious process. Iron with-holding, including sequestration inside tissue macrophages, is considered an important strategy to fight infection. However, for intra-macrophagic pathogens, such as Mycobacterium avium, host defence may depend on intracellular iron sequestration mechanisms. Ferritin, the major intracellular iron storage protein, plays a critical role in this process. In the current study, we studied ferritin expression in mouse bone marrow-derived macrophages upon infection with M. avium. We found that H-ferritin is selectively increased in infected macrophages, through an up-regulation of gene transcription. This increase was mediated by the engagement of Toll like receptor-2, and was independent of TNF-alpha or nitric oxide production. The formation of H-rich ferritin proteins and the consequent iron sequestration may be an important part of the panoply of antimicrobial mechanisms of macrophages.铁元素是决定感染进程结局的关键因素，对宿主与病原体的存活均至关重要。铁扣留策略——包括将铁封存于组织巨噬细胞内——被认为是对抗感染的重要手段。然而对于胞内寄生在巨噬细胞内的病原体（如鸟分枝杆菌（Mycobacterium avium））而言，宿主的防御机制可能依赖于细胞内铁封存途径。铁蛋白（ferritin）作为细胞内主要的铁储存蛋白，在此过程中发挥关键作用。本研究针对鸟分枝杆菌感染后的小鼠骨髓来源巨噬细胞内的铁蛋白表达情况展开了分析。研究发现，感染状态下的巨噬细胞会通过上调基因转录水平，选择性升高H型铁蛋白（H-ferritin）的表达量。该表达上调过程由Toll样受体2（Toll-like receptor 2，TLR2）的激活所介导，且不依赖于肿瘤坏死因子-α（TNF-α）或一氧化氮的产生。富含H型亚基的铁蛋白复合物形成及其后续的铁封存作用，或许是巨噬细胞抗菌防御机制谱系中的重要一环。