DIETARY iron deficiency during influenza infection may leave memory T cells numerically intact yet functionally weakened.
Dietary Iron Deficiency Alters T Cell Memory
The investigators used a murine model of dietary iron deficiency to examine how iron availability shapes memory T cell responses after influenza infection. Mice maintained on an iron deficient diet developed low systemic iron levels and significant anemia, along with higher baseline expression of the transferrin receptor CD71 on T cells, consistent with an increased drive to acquire iron. When challenged with primary influenza infection, these iron deficient animals experienced greater weight loss than iron replete controls, yet still generated antigen specific T cell responses.
Functional Impairment After Influenza Infection
Following recovery from influenza infection, dietary iron deficiency had a pronounced impact on the quality of memory T cells, particularly within the lung. Influenza specific memory CD8+ T cells formed under iron deficient conditions showed reduced effector function, with impaired production of interferon gamma and tumor necrosis factor alpha. Importantly, this cytokine defect persisted even when memory CD8+ T cells were co cultured with iron replete dendritic cells, suggesting that nutritional iron deficiency imprints an intrinsic, long lasting functional impairment on the memory T cell compartment.
Implications for Patients with Iron Deficiency
Although these data come from a murine model, they highlight dietary iron deficiency as a potential modifier of antiviral immunity that may not be apparent from T cell counts alone. The work suggests that patients with chronic nutritional iron deficiency or anemia could form memory T cells that appear numerically adequate yet have weakened effector responses in tissues that matter most for respiratory viral control, such as the lung. For clinicians, the study reinforces the importance of recognizing and addressing dietary iron deficiency as part of holistic strategies to protect at risk populations from influenza and other infections that rely heavily on robust memory T cell function.
Reference: Bradley M et al. Dietary iron deficiency impairs effector function of memory T cells following influenza infection. The Journal of Immunology. 2025;doi:10.1093/jimmun/vkaf291.
