Author(s): ,
Francesca Vinchi
Iron Research Program,New York Blood Center,New York,United States
Richard Sparla
Iron Homeostasis Group,University Hospital Heidelberg,Heidelberg,Germany
Heike Weidner
University Hospital Dresden,Dresden,Germany
Martina Rauner
University Hospital Dresden,Dresden,Germany
Uwe Platzbecker
University Hospital Dresden,Dresden,Germany
Martina Muckenthaler
Iron homeostasis group,University Hospital Heidelberg,Heidelberg,Germany
EHA Learning Center. Vinchi F. Jun 15, 2018; 215928
Topic: 4C Infectious complications
Dr. Francesca Vinchi
Dr. Francesca Vinchi

Access to EHA Members only content is an EHA membership benefit. Click here to join EHA or renew your membership here.

Discussion Forum (0)
Rate & Comment (0)

Abstract: S152


Type: Presidential Symposium


Presentation during EHA23: On Friday, June 15, 2018 from 16:30 - 16:45


Location: Room A1




Chronic iron overload is common in thalassemia (thal), sickle cell disease (SCD) and myelodysplastic syndromes (MDS), due to red blood cell transfusions and increased intestinal iron absorption to support ineffective erythropoiesis.


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. Likewise, transfusional iron overload may impact on the innate immune response, in particular on macrophage function.






We aimed to study the impact of transfusions on the phenotypic plasticity of monocytes and macrophages and their responses to infectious cues.






The functionality of hepatic and splenic macrophages as well as of recruited monocytes was studied in transfused and non-transfused wild-type and myelodysplastic mice, subjected or not to LPS challenge.






Repeated transfusions of fresh RBCs in mice cause macrophage iron overload and cell death as well as recruitment of monocytes to the liver and spleen.


After transfusion, macrophages acquire an M2-like anti-inflammatory phenotype, hallmarked by elevated expression of M2 markers (CD206, Arg-1, Ym1) and reduced expression of M1 markers (MHCII, CD86). Consistently, pro-inflammatory cytokines (IL-6, CCL2, INFg, IL1b) are reduced compared to steady-state levels and anti-inflammatory cytokines (IL-10, IL-4) increased. These results indicate that transfusion-induced erythrophagocytosis likely suppresses the inflammatory response. These findings contrast previous observations, which support a pro-inflammatory role of free heme and iron on macrophage activation. This indicates that not only iron overload but also the route of iron acquisition (e.g. RBC phagocytosis vs free iron uptake) may shape the macrophage phenotype.


After LPS challenge (15hours), macrophages from both transfused and non-transfused mice show an upregulation of M1 markers and pro-inflammatory cytokines. Nevertheless, M1 marker expression is drastically reduced and M2 markers increased in cells isolated from transfused compared to non-transfused mice. This is further reflected by reduced levels of circulating inflammatory cytokines. Our in vivo experiments support the concept that 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 findings do not only apply to wild-type mice but also to a mouse model of transfusion-dependent myelodysplastic syndrome.






Our data provide evidence that transfusions show a negative impact on the innate immune system and blunt the inflammatory response of macrophages to infectious stimuli. Our observations indicate that transfusions dampen macrophage immune effector functions by inducing their switching towards an anti-inflammatory phenotype, which is unlikely to efficiently counteract infections. The weak pro-inflammatory response of the macrophage might contribute to the increased propensity of transfused patients to develop infections, having potential implications for conditions associated with chronic transfusions, as in MDS, thalassemia and SCD.


Finally 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. The underlying mechanisms are currently under investigation.




Session topic: 30. Iron metabolism, deficiency and overload


Keyword(s): Infection, iron overload, Macrophage, transfusion

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.

Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.

Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.

Save Settings