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(Journal of Leukocyte Biology. 2007;81:393-400.)
© 2007 by Society for Leukocyte Biology

The struggle for iron: gastrointestinal microbes modulate the host immune response during infection

Troy A. Markel^*, Paul R. Crisostomo^*, Meijing Wang^*, Christine M. Herring^*, Kirstan K. Meldrum^*, Keith D. Lillemoe^* and Daniel R. Meldrum^*,,,1

^* Departments of Surgery and
Cellular and Integrative Physiology, and
Center for Immunobiology, Indiana University School of Medicine, Indianapolis, Indiana, USA

¹ Correspondence: Departments of Surgery and Cellular and Integrative Physiology and Center for Immunobiology, Indiana University School of Medicine, 545 Barnhill Drive, Emerson Hall 215, Indianapolis, IN 46202, USA. E-mail: dmeldrum{at}iupui.edu

The gastrointestinal track is one source of potential bacterial entry into the host, and the local immune system at the mucosal border is paramount in establishing host immune tolerance and the immune response to invading organisms. Macrophages use iron for production of hydroxy-radical and superoxide reactions, which are necessary for microbial killing. Presumably, as a survival strategy, bacteria, which also require iron for survival, have adapted the ability to sequester iron from the host, thereby limiting the availability to macrophages. As current modes of antimicrobial therapy are evolving, examination of nontraditional therapies is emerging. One such potential therapy involves altering the bacterial micronutrient iron concentration. Necrotizing enterocolitis is a clinical condition where such a strategy makes intuitive sense. This review will describe the immune response to gastrointestinal infection, the mechanisms that the gastrointestinal system uses to absorb intraluminal iron, and the critical role iron plays in the infectious process.

Key Words: absorption • macrophage • chelation

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