Alveolar macrophages (AM) are critical to defense against respiratory pathogens. This study evaluated cellular iron imbalance to immunometabolism in endotoxin-polarized porcine AMs (PAMs). PAMs collected from five 6-week-old pigs were treated with a basal media, iron chelator, or ferric ammonium citrate to maintain iron replete or induce iron deficiency or overload, respectively. After 24 h treatment, PAMs were challenged with saline or lipopolysaccharide (LPS) for 6 h. Cells were analyzed for gene, protein, and untargeted metabolome. Cytokines were determined in culture media. Data were assessed using two-way ANOVA. Treatments successfully induced iron deficiency and overload. The mRNA of DMT1 and ZIP14 was increased up to 300-fold by LPS, but unaffected by iron. Surprisingly, both iron deprivation and overload attenuated LPS-induced inflammation, showing less TNFα production and lower mRNA of pro- and anti-inflammatory cytokines than iron-replete PAMs. Forty-eight metabolites were altered by either or both main effects. LPS enhanced the glycolysis and polyol pathways. Iron deprivation disrupted the TCA cycle. Iron overload increased intracellular cholesterol. Interestingly, iron deprivation augmented, whereas iron overload diminished, LPS-induced itaconic acid production, which has anti-microbial and anti-inflammatory properties. Therefore, iron-deficient PAMs may be more resistant to intracellular pathogens which use PAMs as a conduit for infection.

Pregnant women and children are vulnerable to vitamin A deficiency (VAD), which is often compounded by concurrent deficiencies in other micronutrients, particularly iron and zinc, in developing countries. The study investigated the effects of early-life VAD on motor and cognitive development and trace mineral status in a mouse model. C57BL/6J dams were fed either a vitamin A-adequate (VR) or -deficient (VD) diet across two consecutive gestations and lactations. Offspring from both gestations (G1 and G2) continued the same diets until 6 or 9 weeks of age. Behavioral assays were conducted to evaluate motor coordination, grip strength, spatial cognition, and anxiety. Hepatic trace minerals were analyzed. A VD diet depleted hepatic retinoids and reduced plasma retinol across all ages and gestations. Retracted rear legs and abnormal gait were the most common clinical manifestations observed in VD offspring from both gestations at 9 weeks. Poor performance on the Rotarod test further confirmed their motor dysfunction. VAD didnt affect hemoglobin levels and had no consistent effect on hepatic trace mineral concentrations. These findings highlight the critical role of vitamin A in motor development. There was no clear evidence that VAD alters the risk of iron deficiency anemia or trace minerals.