The nature of extracellular iron influences iron acquisition by Mycobacterium tuberculosis residing within human macrophages.
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.
Olakanmi
Oyebode
O
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.
Schlesinger
Larry S
LS
Ahmed
Ambar
A
Britigan
Bradley E
BE
D002478:Cells, Cultured; D002951:Citrates / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism*; D008264:Macrophages / Q000382:microbiology*; D009169:Mycobacterium tuberculosis / Q000378:metabolism* / Q000472:pathogenicity; D010587:Phagocytosis; D010588:Phagosomes / Q000382:microbiology; D014376:Tuberculosis / Q000382:microbiology
D002951:Citrates; D007371:Interferon-gamma; D007501:Iron; D007781:Lactoferrin