This work was supported in part by NIH Grants K08-HL103756 (to EAH) and U01-HD064827 (to SLS) and a Louis V. Gerstner Scholars Award (to EAH).
Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice
Version of Record online: 19 MAY 2014
© 2014 AABB
Volume 54, Issue 11, pages 2842–2851, November 2014
How to Cite
Prestia, K., Bandyopadhyay, S., Slate, A., Francis, R. O., Francis, K. P., Spitalnik, S. L., Fidock, D. A., Brittenham, G. M. and Hod, E. A. (2014), Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice. Transfusion, 54: 2842–2851. doi: 10.1111/trf.12712
- Issue online: 10 NOV 2014
- Version of Record online: 19 MAY 2014
- Manuscript Accepted: 13 MAR 2014
- Manuscript Revised: 14 FEB 2014
- Manuscript Received: 27 NOV 2013
- NIH. Grant Numbers: K08-HL103756, U01-HD064827
- Louis V. Gerstner Scholars Award
Although human red blood cell (RBC) units may be refrigerator stored for up to 42 days, transfusion of older RBCs acutely delivers a large bolus of iron to mononuclear phagocytes. Similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. Finally, malaria infection continuously delivers iron to macrophages by intra- and extravascular hemolysis. Studies suggest that iron administration increases infectious risk.
Study Design and Methods
To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model Gram-negative intracellular or extracellular pathogens (Salmonella typhimurium or Escherichia coli, respectively), accompanied by RBC transfusion, iron dextran administration, or malarial coinfection.
In our mouse models, transfusion of older RBCs exacerbates infection with both Gram-negative pathogens. Although iron dextran exacerbates E. coli infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with S. typhimurium. Coinfection of mice with Plasmodium yoelii and S. typhimurium produces overwhelming Salmonella sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on E. coli infection of both older RBC transfusion and iron dextran administration.
Transfusion of older RBCs exacerbates Gram-negative infection to a similar extent as malaria coinfection or iron dextran administration. Appropriate antibiotic therapy abrogates the effect of older RBC transfusions on infection with E. coli. Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of RBC transfusions.