Heme Metabolism and Host Defense: Cross Signals During Macrophage Activation

Presenter: Dr. Janet Lee

Macrophages are main effectors of heme metabolism, increasing transiently in the liver during heightened disposal of damaged or senescent red blood cells (sRBC). Macrophages are also essential in defense against microbial threats, but pathologic states of heme excess may be immunosuppressive. Dr. Lee and her lab have uncovered a mechanism whereby an acute rise in sRBC disposal by macrophages led to an immunosuppressive signal in the liver following Klebsiella pneumoniae respiratory infection with deleterious consequences for the host.

Background reading:

• Host-pathogen interactions focusing on Klebsiella pneumoniae infection: Finding Order in the Chaos: Outstanding Questions in Klebsiella pneumoniae Pathogenesis
• Novel K. pneumoniae in vitro assay to assess immune capacity in critical illness: Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness
• Disruption of heme-iron homeostasis leading to immune dysregulation during K. pneumoniae infection: Stressed erythrophagocytosis induces immunosuppression during sepsis through heme-mediated STAT1 dysregulation