Department of Cancer Research and Molecular Medicine, Norges Teknisk-Naturvitenskapelige Universitet, and St. Olavs Hospital, Trondheim, Norway.
J Infect Dis. 2010 Mar;201(5):783-92. doi: 10.1086/650493.
Iron is an essential nutrient for microbes, and many pathogenic bacteria depend on siderophores to obtain iron. The mammalian innate immunity protein lipocalin 2 (Lcn2; also known as neutrophil gelatinase-associated lipocalin, 24p3, or siderocalin) binds the siderophore carboxymycobactin, an essential component of the iron acquisition apparatus of mycobacteria. Here we show that Lcn2 suppressed growth of Mycobacterium avium in culture, and M. avium induced Lcn2 production from mouse macrophages. Lcn2 also had elevated levels and initially limited the growth of M. avium in the blood of infected mice but did not impede growth in tissues and during long-term infections. M. avium is an intracellular pathogen. Subcellular imaging of infected macrophages revealed that Lcn2 trafficked to lysosomes separate from M. avium, whereas transferrin was efficiently transported to the mycobacteria. Thus, mycobacteria seem to reside in the Rab11(+) endocytic recycling pathway, thereby retaining access to nutrition and avoiding endocytosed immunoproteins like Lcn2.
铁是微生物必需的营养物质，许多病原菌依赖于铁载体来获取铁。哺乳动物先天免疫蛋白脂联素 2（Lcn2；也称为中性粒细胞明胶酶相关载脂蛋白、24p3 或亚铁传递蛋白）与铁获取装置的必需成分分枝杆菌羧基麦康丁结合。在这里，我们表明 Lcn2 抑制分枝杆菌在培养物中的生长，并且分枝杆菌诱导来自小鼠巨噬细胞的 Lcn2 产生。Lcn2 在感染小鼠的血液中也具有升高的水平并最初限制分枝杆菌的生长，但不会阻碍组织中的生长和长期感染。分枝杆菌是一种细胞内病原体。受感染的巨噬细胞的亚细胞成像显示 Lcn2 转运到与分枝杆菌分离的溶酶体中，而转铁蛋白则被有效地转运到分枝杆菌中。因此，分枝杆菌似乎位于 Rab11(+) 内体再循环途径中，从而保留对营养物质的获取并避免内吞免疫蛋白如 Lcn2。
