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

Sophie Austermeier
Mark S Gresnigt
Alexandra Hähnlein
Kira Skurk

Publications

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.
Bruno M, Dewi IMW, Matzaraki V, Ter Horst R, Pekmezovic M, Rösler B, Groh L, Röring RJ, Kumar V, Li Y, Carvalho A, Netea MG, Latgé JP, Gresnigt MS, van de Veerdonk FL (2021) Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways. Comput Struct Biotechnol J 19, 647-663.
Bruno M, Horst R, Pekmezovic M, Kumar V, Li Y, Netea MG, Latgé JP, Gresnigt MS, van de Veerdonk FL (2021) Data of common and species-specific transcriptional host responses to pathogenic fungi. Data Brief 35, 106928.
Cavalli G, Tengesdal IW, Gresnigt M, Nemkov T, Arts RJW, Domínguez-Andrés J, Molteni R, Stefanoni D, Cantoni E, Cassina L, Giugliano S, Schraa K, Mills TS, Pietras EM, Eisenmensser EZ, Dagna L, Boletta A, D'Alessandro A, Joosten LAB, Netea MG, Dinarello CA (2021) The anti-inflammatory cytokine interleukin-37 is an inhibitor of trained immunity. Cell Rep 35(1), 108955.
Dewi IMW, Cunha C, Jaeger M, Gresnigt MS, Gkountzinopoulou ME, Garishah FM, Duarte-Oliveira C, Campos CF, Vanderbeke L, Sharpe AR, Brüggemann RJ, Verweij PE, Lagrou K, Vande Velde G, de Mast Q, Joosten LAB, Netea MG, van der Ven AJAM, Wauters J, Carvalho A, van de Veerdonk FL (2021) Neuraminidase and SIGLEC15 modulate the host defense against pulmonary aspergillosis. Cell Rep Med 2(5), 100289.
Last A, Maurer M, Mosig AS, Gresnigt MS, Hube B (2021) In vitro infection models to study fungal-host interactions. FEMS Microbiol Rev , fuab005.
Pekmezovic M, Hovhannisyan H, Gresnigt MS, Iracane E, Oliveira-Pacheco J, Siscar-Lewin S, Seemann E, Qualmann B, Kalkreuter T, Müller S, Kamradt T, Mogavero S, Brunke S, Butler G, Gabaldón T, Hube B (2021) Candida pathogens induce protective mitochondria-associated type I interferon signalling and a damage-driven response in vaginal epithelial cells. Nat Microbiol 6(5), 643-657.
Austermeier S, Kasper L, Westman J, Gresnigt MS (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. (Review)

Funding