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

Publications

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.
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.
Chao YY, Puhach A, Frieser D, Arunkumar M, Lehner L, Seeholzer T, Garcia-Lopez A, van der Wal M, Fibi-Smetana S, Dietschmann A, Sommermann T, Ćiković T, Taher L, Gresnigt MS, Vastert SJ, van Wijk F, Panagiotou G, Krappmann D, Groß O, Zielinski CE (2023) Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation. Nat Immunol 24(2), 295-308.
Lange T, Kasper L, Gresnigt MS, Brunke S, Hube B (2023) "Under Pressure" - How fungi evade, exploit, and modulate cells of the innate immune system. Semin Immunol 66, 101738. (Review)
Matzaraki V, Beno A, Jaeger M, Gresnigt MS, Keur N, Boahen C, Cunha C, Gonçalves SM, Leite L, Lacerda JF, Campos A, van de Veerdonk FL, Joosten L, Netea MG, Carvalho A, Kumar V (2022) Genetic determinants of fungi-induced ROS production are associated with the risk of invasive pulmonary aspergillosis. Redox Biol 55, 102391.
Pekmezovic M, Dietschmann A, Gresnigt MS (2022) Type I interferons during host-fungus interactions: Is antifungal immunity going viral? PLOS Pathog 18(8), e1010740.
Akoumianaki T, Vaporidi K, Diamantaki E, Pène F, Beau R, Gresnigt MS, Gkountzinopulou M, Venichaki M, Drakos E, El-Benna J, Samonis G, Le KTT, Kumar V, Georgopoulos D, van de Veerdonk FL, Netea MG, Latge JP, Chamilos G (2021) Uncoupling of IL-6 signaling and LC3-associated phagocytosis drives immunoparalysis during sepsis. Cell Host Microbe 29(8), 1277-1293.
Alonso-Monge R, Gresnigt MS, Román E, Hube B, Pla J (2021) Candida albicans colonization of the gastrointestinal tract: A double-edged sword. PLOS Pathog 17(7), e1009710.
Austermeier S, Pekmezović M, Porschitz P, Lee S, Kichik N, Moyes DL, Ho J, Kotowicz NK, Naglik JR, Hube B, Gresnigt MS (2021) Albumin neutralizes hydrophobic toxins and modulates Candida albicans pathogenicity. mBio 12(3), e0053121.

Funding