Chronic transfusions turn macrophages anti-inflammatory
Chronically transfused patients show increased susceptibility to infections. Iron overload may increase the risk of infections by supporting bacterial growth and altering the response of the adaptive immunity. Dr. Francesca Vinchi (New York Blood Center, New York, USA) is particularly interested in pathological conditions with chronic iron overload in macrophages, such as thalassemia, sickle cell disease (SCD) and myelodysplastic syndrome (MDS). How does iron overload shape macrophage phenotype?
To answer this, mice were subjected to repeated transfusions with fresh erythrocytes and this induced M2 anti-inflammatory liver macrophages. Together with LPS-stimulation this blunted pathogen-associated molecular pattern (PAMP)-mediated inflammation and suppressed the release of M1 inflammatory cytokines induced by PAMP.
On the other hand, both iron and heme triggered sterile inflammation and promoted immune-mediated tissue damage by inducing M1 inflammatory macrophages. Hemopexin, the plasma protein with the highest binding affinity for heme, dampened sterile inflammation by preventing heme-triggered M1-polarization.
Vinchi: “Our in vivo experiments support a dual role of iron overload in macrophage functional response. Transfusions shape macrophages towards an M2-like anti-inflammatory phenotype after LPS stimulation, highlighting a novel adverse anti-inflammatory effect of transfusions upon infections. These results suggest that transfusion practice might increase the risk of infections not solely by promoting the growth of microorganisms through increasing iron availability, but also by impairing the innate immune system, through the alteration of macrophage plasticity.”