The Macrophage Iron Signature in Health and Disease

Abstract

Throughout life, macrophages are located in every tissue of the body, where their main roles are to phagocytose cellular debris and recycle aging red blood cells. In the tissue niche, they promote homeostasis through trophic, regulatory, and repair functions by responding to internal and external stimuli. This in turn polarizes macrophages into a broad spectrum of functional activation states, also reflected in their iron-regulated gene profile. The fast adaptation to the environment in which they are located helps to maintain tissue homeostasis under physiological conditions.

Iron dyshomeostasis and time-course changes in iron-uptake systems and ferritin level in relation to pro-inflammatory microglia polarization in sepsis-induced encephalopathy

“…Moreover, polarization to an antiinflammatory state was associated with arginase 1 upregulation and increased nitric oxide production, which could support Frontiers in Physiology frontiersin.org mitochondrial respiration and limit the glycolytic response and acidosis, subsequently resulting in a decrease in iron uptake and increase in iron efflux (Carr et al, 2020;McCarthy et al, 2018b). Iron status is also critically determinant of IL-1β and TNF-α release from microglia through the modulation of NF-κB and mitochondrial OXPHOS (Xia et al, 2021;Daglas and Adlard, 2018), thus creating a positive feedback loop that leads to chronic neuroinflammation (Di Paola et al, 2021;Zhu et al, 2015;Mertens et al, 2021). In vitro, the transformation of macrophages into the M1 phenotype can be accelerated by the presence of iron.…”

Diverse Cell Death Mechanisms Are Simultaneously Activated in Macrophages Infected by Virulent Mycobacterium tuberculosis

“…The activation of immune cells during infection is necessary to eliminate pathogens [ 2 ]. Macrophages are one of the first cells activated in response to an infection; their precursor cells are circulating monocytes, which migrate into the tissue and are differentiated into resident macrophages [ 3 ].…”

Questioning Established Theories and Treatment Methods Related to Iron and Other Metal Metabolic Changes, Affecting All Major Diseases and Billions of Patients

“…The targeting of specific mechanisms and pathways involving iron and other metal ion abnormalities is important for many diseases. An example is the major role of macrophages in the abnormal distribution and deposition of iron in many malignant, inflammatory and infectious diseases including COVID-19, which in most cases is also characterized by an elevation in serum ferritin and a reduction in serum iron levels [62][63][64][65][66][67]. The mechanisms involved in these changes are not yet fully clarified.…”