Can Iron Storage Disease Be Induced by a Chronic Infection Such As Tuberculosis in Asian Elephants (Elephas maximus)?
Iron storage disease (ISD) is a major concern for zoological breeding programs of many endangered species. In human medicine, ISD is divided in primary hemosiderosis and secondary hemosiderosis. Primary hemosiderosis tends to reflect genetic predisposition, whereas secondary hemosiderosis is usually infectious in origin and plays an important part in the immune response. We investigated severe iron depositions in several organs in three Asian elephants (Elephas maximus) suffering from Mycobacterium tuberculosis infection.
Three animals suspected to be infected with tuberculosis were euthanized due to severe and multiple health problems. Pathological examination revealed typical M. tuberculosis lesions in lung and lymph nodes. Culture and RT-PCR analysis performed from the lesions, of post-mortally collected tracheal secretions and of stomach wall tissues confirmed M. tuberculosis infection. Sequencing of the cultures demonstrated a single source of infection, most likely a human1 one. Spleens showed severe, lung moderate and liver mild iron depositions, mainly in macrophages. By qPCR measuring mRNA of hepcidin, the iron regulating hormone, and IL-6 which stimulates hepcidin transcription, we found decreased CT values of hepcidin between animals with low versus high iron storage from 26.62 to 21.09 ng/ml (p=0.004) and of IL-6 from 36.14 to 33.27 ng/ml (p=0.002). This means mRNA synthesis of hepcidin and IL-6 was increased, and a likely cause of the increased iron deposition in macrophages throughout the body.
This is the first demonstration of a secondary hemosiderosis in Asian elephants and provides evidence that ISD plays an important role in the immunoreaction in chronic granulomatous inflammation caused by infectious agent.
1. Ghielmetti G, Coscolla M, Ruetten M, Friedel U, Loiseau C, Feldmann J, Steinmetz HP, Stucki D, Gagneux S. Tuberculosis in Swiss captive Asian elephants: microevolution of Mycobacterium tuberculosis characterized by multilocus variable-number tandem-repeat analysis and whole-genome sequencing. Scientific Reports. 2017;7:14647.