Immunology of Fungal Infections

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-ɣ 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.

Macrophage engulfing multiple Candida albicans yeast

Staff

Karen Cheng
Beatriz Cristovão
Axel Dietschmann
Mark Gresnigt
Dolly Estella Montaño Espinosa
Jördis Schuchardt
Ann-Kathrin Zimmermann

Publications

Gonçalves SM, Leite L, de Vasconcelos P, Pereira I, Dewi IMW, Mercier T, Aerts R, Ligeiro D, Mendes F, Freitas F, Condeço J, Vieira J, Espada E, Lagrou K, Maertens JA, Gresnigt MS, Dinarello CA, Lacerda JF, Vaz CP, Cunha C, Carvalho A, van de Veerdonk FL (2025) A functional polymorphism in IL-36β modulates macrophage antifungal effector functions and increases susceptibility to invasive pulmonary Aspergillosis. J Infect Dis [Accepted]
Rosati D, Valentine M, Bruno M, Pradhan A, Dietschmann A, Jaeger M, Leaves I, van de Veerdonk FL, Joosten LAB, Roy S, Stappers MHT, Gow NAR, Hube B, Brown AJP, Gresnigt MS, Netea MG (2025) Lactic acid in the vaginal milieu modulates the Candida-host interaction. Virulence 16(1), 2451165.
Valentine M, Rosati D, Dietschmann A, Schille TB, Netea MG, Hube B, Gresnigt MS (2025) Probiotic Lactobacillus species modulate immune responses during vaginal epithelial cell colonization. J Infect Dis , jiaf221.
Valentine M, Wilson D, Gresnigt MS, Hube B (2025) Vaginal Candida albicans infections: host-pathogen-microbiome interactions. FEMS Microbiol Rev 49, fuaf013.
Cheng KO, Montaño DE, Zelante T, Dietschmann A, Gresnigt MS (2024) Inflammatory cytokine signalling in vulvovaginal candidiasis: a hot mess driving immunopathology. Oxf Open Immunol 5(1), iqae010. (Review)
Jaeger M, Dietschmann A, Austermeier S, Dinçer S, Porschitz P, Vornholz L, Maas RJA, Sprenkeler EGG, Ruland J, Wirtz S, Azam T, Joosten LAB, Hube B, Netea MG, Dinarello CA, Gresnigt MS (2024) Alpha1-antitrypsin impacts innate host-pathogen interactions with Candida albicans by stimulating fungal filamentation. Virulence 15(1), 2333367.
Pekmezović M, Hube B, Gresnigt MS (2024) Pathogenicity strategies of Candida species during interactions with epithelial cells. In: Brakhage AA, Kniemeyer O, Zipfel PF (eds.) The Mycota - Human and Animal Relationships 3. 6, pp. 35-49. Springer, Cham. ISBN: 978-3-031-64852. (Review)
Schaefer S, Vij R, Sprague JL, Austermeier S, Dinh H, Judzewitsch PR, Müller-Loennies S, Lopes Silva T, Seemann E, Qualmann B, Hertweck C, Scherlach K, Gutsmann T, Cain AK, Corrigan N, Gresnigt MS, Boyer C, Lenardon MD, Brunke S (2024) A synthetic peptide mimic kills Candida albicans and synergistically prevents infection. Nat Commun 15(1), 6818.
Schimanski J, Gresnigt MS, Brunner E, Werz O, Hube B, Garscha U (2024) Hyphal-associated protein expression is crucial for Candida albicans-induced eicosanoid biosynthesis in immune cells. Eur J Immunol 54(3), e2350743.
Valentine M*, Rudolph P*, Dietschmann A, Tsavou A, Mogavero S, Lee S, Priest EL, Zhurgenbayeva G, Jablonowski N, Timme S, Eggeling C, Allert S, Dolk E, Naglik JR, Figge MT, Gresnigt MS*#, Hube B*# (2024) Nanobody-mediated neutralization of candidalysin prevents epithelial damage and inflammatory responses that drive vulvovaginal candidiasis pathogenesis. mBio 15(3), e0340923.