Dietary iron overload enhances susceptibility to Yersinia enterocolitica infection

Abstract

Hemochromatosis and hemosiderosis are iron overload disorders that cause immune dysfunction and increase susceptibility to bacterial infections. There have been numerous case studies reporting septic-like outcomes for hemochromatosis patients infected with enteric Yersiniae; however, research regarding hemosiderosis and Yersinia infection is limited. Here, we have established a mouse model of hemosiderosis by feeding C57BL/6 mice a high-iron diet. These mice exhibit several indicators of iron overload that are seen clinically, including elevated serum iron levels and iron deposition in various tissues. Characterization of the iron overload mouse model shows that a high-iron diet induces local inflammation in the small intestine and systemic inflammation in a time-dependent manner. Oral infection with Yersinia enterocolitica causes complete mortality in the iron-overloaded mice, while wild-type mice all survive and effectively clear the infection. Lastly, we have observed that iron chelation therapies such as Deferoxamine and Deferisarox are detrimental to iron-overloaded mice during Yersinia infection. This work provides a model to further study iron overload disorders and Yersinia infection.