Invasive fungal infections rarely occur in healthy hosts, and a compromised immune system is one of the major predisposing factors for invasive fungal disease. Although a wide range of antifungal drugs are available to treat such infections, therapies that aim at improving the immune system are increasingly recognized as essential in improving the outcome of fungal infections. Specifically, modification of immune-cell metabolism and phagocytosis are promising strategies to augment immune cell function.
Interferon-g is a promising candidate due to its capacity to improve macrophage microbicidal activity, and clinical trials are ongoing to explore its potential to improve the outcome of candidemia. In close collaboration with the Department of Microbial Pathogenicity Mechanisms, we investigate how Candida albicans interacts with macrophages that were augmented by immunotherapy. We specifically focus on inflammasome activation and fungal escape from macrophages, which is in part mediated by the fungal toxin candidalysin.
(2020) I want to break free - macrophage strategies to recognize and kill Candida albicans, and fungal counter-strategies to escape. Curr Opin Microbiol 58, 15-23.
(2019) The itaconate pathway is a central regulatory node linking innate immune tolerance and trained immunity. Cell Metab 29(1), 211-220.e5.
(2019) Frontline science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst. J Leukoc Biol 106(1), 11-25.
(2018) Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection. Eur J Clin Microbiol Infect Dis 37(10), 1915-1922.
(2018) The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. Nat Commun 9(1), 4260.