Dietary Iron Plays Key Role in Immune Cell Response

By Irene Yeh 

Iron is an essential mineral to produce hemoglobin and aid immunologic processes, such as cellular activation and proliferation, which are the foundations of the formation of T cell responses. To determine just how much iron levels affect immune responses, a team of researchers from Columbia University Vagelos College of Physicians and Surgeons conducted a study with mice (The Journal of Immunology, DOI: 10.1093/jimmun/vkaf291). It was found that mice with dietary iron deficiency and infected with influenza struggled to produce a key signal needed to fight viruses—and this ability did not return even after iron levels went back to normal. 

Iron Levels and the Effect on Immune Cells 

The research team took two cohorts of mice and supplied them with or without iron in their diets. Both groups were infected with the X31 influenza virus, and their infection morbidity was determined by daily weight recordings. Hemoglobin levels were extracted at the four-week mark, and iron levels were measured at the time of euthanasia via blood samples. T cell numbers were also counted through lung and spleen tissue samples.  

The team confirmed that hemoglobin and liver samples were iron deficient. For T cells, flow cytometry was used to compare mice with normal iron levels and mice that were iron deficient. Overall, the T cells in their spleens and lungs had similar numbers. Even when examining different types of T cells (those that had not yet encountered the influenza virus and those that had some prior immune experience), there were minimal differences in the number of T cells. It was determined that iron deficiency did not largely change T cell activation at baseline. 

However, there were still a few small differences in the T cells’ characteristics. In the iron deficient group, the mice showed that their transferrin receptor—a protein that T cells take iron through—was expressed at a higher level on certain T cells, especially the spleen, which indicates that these cells were trying to compensate low iron levels. Furthermore, the iron deficient mice showed more regulatory T cells in the spleen, which suppresses immune responses, and reduced expression of the CXCR3 receptor, which is linked to inflammatory T cell responses in the lungs.  

Iron Deficiency Leads to Decreased Immune Response 

The results showed that a lack of dietary iron can weaken immune responses and a lower activation of T cells (The Journal of Immunology, DOI: 10.1093/jimmun/vkaf291). Even during recovery, the iron deficient group showed increased numbers of influenza-specific T cells but were not working as well. Memory T cells in iron deficient mice also had the decreased ability to produce anti-viral cytokines. These issues continued even after the T cells were given ideal conditions to respond, which suggests that iron deficiency causes lasting damage to T cell function. Most importantly, this indicates that T cells require adequate iron in order to activate and work properly. 

Though iron deficient mice showed increased morbidity, the study did not conclusively determine if it was caused by poor nutritional status or the inability to clear the virus. Other limitations included not being able to identify how iron affects the way the immune system recognizes germs and the environment inside the tissues, both of which are important for building long-lasting immune protection. The team was also not able to discern whether weakened immune cells found in the lungs came from the bloodstream or cells that were already living in the lung tissue. More understanding is required on how iron deficiency affects the body’s ability to clear viruses, how immune cells develop and change, when these problems begin, and whether immune memory formed during low-iron periods has lasting effects.  

Nonetheless, the study provides insights into the fundamental role iron plays in immune responses. Improving iron levels, especially during childhood, can strength immune systems for the long run. As iron deficiency is a common condition on a global scale, this study sheds light on the importance of adequate nutrition and providing resources to those who need it.