Interaction with immune cells

Phagocytes such as macrophages and neutrophils are key players of the innate immune system and represent a crucial line of defense against pathogenic Candida species such as C. albicans and C. glabrata. This is particularly illustrated by the fact that invasive Candida infections rarely occur in healthy hosts, and a compromised immune system is one of the major predisposing factors for disease.

Recognition of Candida cells by phagocytes leads to cytokine production, phagocytosis, and the activation of antimicrobial effector functions to induce killing of the fungus. On the other hand, pathogenic Candida spp. are well adapted to their host and have developed mechanisms to evade or counteract the anti-microbial activities of phagocytes. One of these mechanisms is the adaptation of fungal metabolism to cope with nutrient limitation inside the phagosome. This and other strategies allow C. albicans and C. glabrata to not only survive phagocytosis by macrophages, but even proliferate intracellularly and escape. C. albicans escapes by rapid hyphal growth and host cell damage. In contrast, C. glabrata replicates as yeast cells inside macrophages and persists for days, before macrophages burst and fungal cells are released.

We want to characterize the interaction of C. albicans, C. glabrata, and C. auris with phagocytes. We are especially interested in the fungal factors and activities that help Candida to cope with these immune cells, survive and escape. Moreover, in close collaboration with the Junior Research Group Adaptive Pathogenicity Strategies we investigate how immunotherapy impacts on the interactions between C. albicans and macrophages and mitigates escape of C. albicans from macrophages. Therapies that aim at improving the innate immune system are increasingly recognized as essential in improving the outcome of fungal infections. Particularly interferon-γ is a promising candidate due to its potential of improving macrophage microbicidal activity.

Staff

Sophie Austermeier
Mark Gresnigt
Lydia Kasper
Annika König

Publications

Westman J, Hube B, Fairn GD (2019) Integrity under stress: Host membrane remodelling and damage by fungal pathogens. Cell Microbiol 21(4), e13016.
Assendorp EL, Gresnigt MS, Sprenkeler EGG, Meis JF, Dors N, van der Linden JWM, Henriet SSV (2018) Adjunctive interferon-γ immunotherapy in a pediatric case of Aspergillus terreus infection. Eur J Clin Microbiol Infect Dis 37(10), 1915-1922.
Kasper L, König A, Koenig PA, Gresnigt MS, Westman J, Drummond RA, Lionakis MS, Groß O, Ruland J, Naglik JR, Hube B (2018) The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. Nat Commun 9(1), 4260.
Verma AH, Zafar H, Ponde NO, Hepworth OW, Sihra D, Aggor FEY, Ainscough JS, Ho J, Richardson JP, Coleman BM, Hube B, Stacey M, McGeachy MJ, Naglik JR, Gaffen SL, Moyes DL (2018) IL-36 and IL-1/IL-17 drive immunity to oral candidiasis via parallel mechanisms. J Immunol 201(2), 627-634.
Cassone A, Vecchiarelli A, Hube B (2016) Aspartyl proteinases of eukaryotic microbial pathogens: From eating to heating. PLOS Pathog 12(12), e1005992. (Review)
Gabrielli E, Sabbatini S, Roselletti E, Kasper L, Perito S, Hube B, Cassone A, Vecchiarelli A, Pericolini E (2016) In vivo induction of neutrophil chemotaxis by secretory aspartyl proteinases of Candida albicans. Virulence 7(7), 819-825.
Hellwig D, Voigt J, Bouzani M, Löffler J, Albrecht-Eckardt D, Weber M, Brunke S, Martin R, Kurzai O, Hünniger K (2016) Candida albicans induces metabolic reprogramming in human NK cells and responds to perforin with a Zinc depletion response. Front Microbiol 7, 750.
Gabrielli E, Pericolini E, Luciano E, Sabbatini S, Roselletti E, Perito S, Kasper L, Hube B, Vecchiarelli A (2015) Induction of Caspase-11 by aspartyl proteinases of Candida albicans and implication in promoting inflammatory response. Infect Immun 83(5), 1940-1948.
Kasper L, Seider K, Hube B (2015) Intracellular survival of Candida glabrata in macrophages: immune evasion and persistence. FEMS Yeast Res 15(5), fov042.
Brunke S, Seider K, Fischer D, Jacobsen ID, Kasper L, Jablonowski N, Wartenberg A, Bader O, Enache-Angoulvant A, Schaller M, d’Enfert C, Hube B (2014) One small step for a yeast - Microevolution within macrophages renders Candida glabrata hypervirulent due to a single point mutation. PLOS Pathog 10(10), e1004478.

Funding