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

Science Translational Medicine
Joe L HsuMark R Nicolls

Abstract

Invasive pulmonary disease due to the mold Aspergillus fumigatus can be life-threatening in lung transplant recipients, but the risk factors remain poorly understood. To study this process, we used a tracheal allograft mouse model that recapitulates large airway changes observed in patients undergoing lung 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 (ΔsreA/ΔcccA) was lower than that of the wild-type mold. Alloimmune-mediated microvascular damage and iron overload did not appear to im...Continue Reading

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Citations

Nov 1, 2018·Current Opinion in Infectious Diseases·Efthymia I MatthaiouJoe L Hsu
Feb 26, 2019·Transplantation·Christian HeimStephan M Ensminger
Nov 15, 2019·Clinical Microbiology Reviews·Jean-Paul Latgé, Georgios Chamilos
Jan 6, 2019·Pharmaceuticals·Joana NevesMartina U Muckenthaler
Mar 12, 2020·Frontiers in Cellular and Infection Microbiology·Changsheng JiangQigai He
Mar 16, 2021·Frontiers in Cellular and Infection Microbiology·Laura-Isobel McCall
Oct 13, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Matthias MisslingerHubertus Haas

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