HFE and Iron deficiency anemia: Subsequently, impaired TLR-4-signaling involving the TRIF (Tir domain-containing adaptor inducing interferon-beta (Ticam1))/TRAM (Trif-related adaptor molecule (Ticam2)) step has been proposed as the underlying mechanism and suggested to be caused by intracellular iron deficiency of Hfe-deficient macrophages [10].