Macrophages: a Trojan horse in COVID-19?

(encoded by Slc40a1), the authors next looked at the role of ferroportin in the intestine. Mice expressing a hepcidin-resistant ferroportin variant (Slc40a1C326Y) specifically in macrophages and neutrophils had impaired intestinal repair after DSS withdrawal, which indicates that these cells are a crucial target for cDC-derived hepcidin in the gut. So what is the mechanism of hepcidin-mediated intestinal repair? Hamp∆CD11C mice had higher levels of non-haem iron in the intestinal lumen after DSS administration than control mice. This likely reflects, in the absence of hepcidin, the ferroportin-mediated efflux of iron from intestinal macrophages that have phagocytosed erythrocytes. The extracellular iron chelator deferox amine restored mucosal repair after DSS withdrawal in Hamp∆CD11C mice. In keeping with the known role of iron in modulating microbial populations, Hamp∆CD11C mice had altered composition of the intestinal microbiota with increased levels of tissue-infiltrating bacteria, and faecal microbiota transplantation from Hamp∆CD11C mice to wild-type germ-free mice transferred the impaired intestinal repair phenotype. Thus, hepcidin production by intestinal DCs in response to microbial signals limits iron levels in the intestinal lumen, which restrains tissue infiltration by the microbiota to promote intestinal repair.