Olakanmi Oyebode, Schlesinger Larry S, Ahmed Ambar, Britigan Bradley E
Department of Internal Medicine and Research Service, VA Medical Center-Iowa City and Department of Internal Medicine, Roy G. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, 52242, USA.
Infect Immun. 2004 Apr;72(4):2022-8. doi: 10.1128/IAI.72.4.2022-2028.2004.
We have reported that Mycobacterium tuberculosis residing within the phagosomes of human monocyte-derived macrophages (MDM) can acquire Fe from extracellular transferrin (TF) and sources within the MDM. In the lung, Fe is also bound to lactoferrin (LF) and low-molecular-weight chelates. We therefore investigated the ability of intraphagosomal M. tuberculosis to acquire Fe from these sources. M. tuberculosis acquired 30-fold and 3-fold more Fe from LF and citrate, respectively, compared to TF, in spite of similar MDM-associated Fe. M. tuberculosis infection decreased MDM-associated Fe relative to uninfected MDM as follows: TF (38.7%), citrate (21.1%), and LF (15.3%). M. tuberculosis Fe acquisition from extracellular chelates (exogenous source) and from endogenous MDM Fe initially acquired from the three chelates (endogenous source) was compared. M. tuberculosis Fe acquisition was similar from exogenous and endogenous sources supplied as Fe-TF. In contrast, there was much greater intracellular M. tuberculosis Fe uptake from LF and citrate from the exogenous than endogenous source. Gamma interferon (IFN-gamma) reduced MDM Fe uptake from each chelate by approximately 50% and augmented the M. tuberculosis-induced decrease in MDM Fe uptake from exogenous TF, but not from LF or citrate. IFN-gamma minimally decreased intracellular M. tuberculosis Fe acquisition from exogenous Fe-TF but significantly increased Fe uptake from LF and citrate. Intraphagosomal M. tuberculosis Fe acquisition from both exogenous and endogenous MDM sources, and the effect of IFN-gamma on this process, is influenced by the nature of the extracellular Fe chelate. M. tuberculosis has developed efficient mechanisms of acquiring Fe from a variety of Fe chelates that it likely encounters within the human lung.
我们曾报道，存在于人类单核细胞衍生巨噬细胞（MDM）吞噬小体中的结核分枝杆菌能够从细胞外转铁蛋白（TF）以及MDM内的来源获取铁。在肺中，铁还与乳铁蛋白（LF）和低分子量螯合物结合。因此，我们研究了吞噬小体内的结核分枝杆菌从这些来源获取铁的能力。尽管MDM相关铁含量相似，但结核分枝杆菌从LF和柠檬酸盐中获取的铁分别比从TF中获取的多30倍和3倍。与未感染的MDM相比，结核分枝杆菌感染使MDM相关铁减少，减少比例如下：TF（38.7%）、柠檬酸盐（21.1%）和LF（15.3%）。比较了结核分枝杆菌从细胞外螯合物（外源来源）和最初从三种螯合物获取的内源性MDM铁（内源来源）中获取铁的情况。作为铁 - TF供应时，结核分枝杆菌从外源和内源来源获取铁的情况相似。相比之下，从外源来源的LF和柠檬酸盐中摄取的细胞内结核分枝杆菌铁比内源来源多得多。γ干扰素（IFN - γ）使MDM从每种螯合物中的铁摄取减少约50%，并增强了结核分枝杆菌诱导的MDM从外源TF中铁摄取的减少，但对LF或柠檬酸盐没有影响。IFN - γ使细胞内结核分枝杆菌从外源铁 - TF中的铁摄取略有减少，但显著增加了从LF和柠檬酸盐中的铁摄取。吞噬小体内的结核分枝杆菌从外源和内源性MDM来源获取铁的情况，以及IFN - γ对这一过程的影响，受细胞外铁螯合物性质的影响。结核分枝杆菌已形成从其在人类肺中可能遇到的多种铁螯合物获取铁的有效机制。
