<i>Anaplasma phagocytophilum</i> Subversion of Host Hepcidin-Ferroportin Iron Nutritional Immunity

Iron is an essential element for both humans and microorganisms, serving as a cofactor in key metabolic processes. Obligatory intracellular bacterium <i>Anaplasma phagocytophilum</i> infects and proliferates within a membrane-bound vacuole ( <i>Aph-</i> vacuoles) of neutrophils and endothelial cells, competitively acquiring intracellular iron from the host. Upon exploration of cytoplasmic labile free iron levels and distribution in the <i>A. phagocytophilum</i> -infected and uninfected host cells, we uncovered the unique ability of this bacterium to enrich intravacuolar iron. Ferroportin is the only cellular iron exporter of the host cells, which is regulated by the hepatic hormone hepcidin. Herein, we investigate the role of ferroportin and endogenous hepcidin locally produced by the host cells for iron enrichment in <i>Aph-</i> vacuoles. Ultimately, this study provides new insights into the novel mechanisms of microbial manipulation of host cells to acquire the essential micronutrient iron and overcoming host nutritional immunity, which may facilitate more effective treatment and prevention.