Aspergillus fumigatus is an opportunistic mould that causes
invasive pulmonary aspergillosis (IPA), a life-threatening
infection in immunocompromised patients. During the course of IPA, localised areas of tissue
hypoxia occur.
Bacterial infection models revealed that hypoxic microenvironments modulate the function of host immune cells. However, the influence of
hypoxia on anti-fungal immunity has been largely unknown. We evaluated the impact of
hypoxia on the human anti-A. fumigatus immune response. Human monocyte-derived dendritic cells (DCs) were stimulated in vitro with germ tubes of A. fumigatus under normoxia or
hypoxia (1% O2 ), followed by analysis of DC viability, maturation and
cytokine release. While DC viability was unaffected,
hypoxia attenuated
cytokine release from DCs and maturation of DCs upon stimulation with A. fumigatus. These data suggest that
hypoxia at the site of A. fumigatus
infection inhibits full activation and function of human DCs. Thereby, this study identified
hypoxia as a crucial immune-modulating factor in the human anti-fungal immune response that might influence the course and outcome of IPA in immunocompromised patients.