[Research Articles] Microhemorrhage-associated tissue iron enhances the risk for Aspergillus fumigatus invasion in a mouse model of airway transplantation

We report that microhemorrhage-related iron content may be a major determinant of A. fumigatus invasion and, consequently, its virulence. Invasive growth was increased during progressive alloimmune-mediated graft rejection associated with high concentrations of ferric iron in the graft. The role of iron in A. fumigatus invasive growth was further confirmed by showing that this invasive phenotype was increased in tracheal transplants from donor mice lacking the hemochromatosis gene (Hfe–/–). The invasive phenotype was also increased in mouse syngrafts treated with topical iron solution and in allograft recipients receiving deferoxamine, a chelator that increases iron bioavailability to the mold. The invasive growth of the iron-intolerant A. fumigatus double-knockout mutant (sreA/cccA) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to impair the host’s immune response. In human lung transplant recipients, positive staining for iron in lung transplant tissue was more commonly seen in endobronchial biopsy sections from transplanted airways than in biopsies from the patients’ own airways. Collectively, these data identify iron as a major determinant of A. fumigatus invasive growth and a potential target to treat or prevent A. fumigatus infections in lung transplant patients.

Source: Science Translational Medicine - February 21, 2018 Category: Biomedical Science Authors: Hsu, J. L., Manouvakhova, O. V., Clemons, K. V., Inayathullah, M., Tu, A. B., Sobel, R. A., Tian, A., Nazik, H., Pothineni, V. R., Pasupneti, S., Jiang, X., Dhillon, G. S., Bedi, H., Rajadas, J., Haas, H., Aurelian, L., Stevens, D. A., Nicolls, M. R. Tags: Research Articles Source Type: research