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

Kasper L, Seider K, Gerwien F, Allert S, Brunke S, Schwarzmüller T, Ames L, Zubiria-Barrera C, Mansour MK, Becken U, Barz D, Vyas JM, Reiling N, Haas A, Haynes K, Kuchler K, Hube B (2014) Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages. PLOS One 9(5), e96015.
Miramón P, Dunker C, Kasper L, Jacobsen ID, Barz D, Kurzai O, Hube B (2014) A family of glutathione peroxidases contributes to oxidative stress resistance in Candida albicans. Med Mycol 52(3), 223-239.
Quintin J, Voigt J, van der Voort R, Jacobsen ID, Verschueren I, Hube B, Giamarellos-Bourboulis EJ, van der Meer JW, Joosten LA, Kurzai O, Netea MG (2014) Differential role of NK cells against Candida albicans infection in immunocompetent or immunocompromised mice. Eur J Immunol 44(8), 2405-2414.
Seider K, Gerwien F, Kasper L, Allert S, Brunke S, Jablonowski N, Schwarzmüller T, Barz D, Rupp S, Kuchler K, Hube B (2014) Immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of Candida glabrata within macrophages. Eukaryot Cell 13(1), 170-183.
Voigt J, Hünniger K, Bouzani M, Jacobsen ID, Barz D, Hube B, Löffler J, Kurzai O (2014) Human natural killer cells acting as phagocytes against Candida albicans and mounting an inflammatory response that modulates neutrophil antifungal activity. J Infect Dis 209(4), 616-626.
Miramón P, Kasper L, Hube B (2013) Thriving within the host: Candida spp. interactions with phagocytic cells. Med Microbiol Immunol 202(3), 183-195. (Review)
Pietrella D, Pandey N, Gabrielli E, Pericolini E, Perito S, Kasper L, Bistoni F, Cassone A, Hube B, Vecchiarelli A (2013) Secreted aspartic proteases of Candida albicans activate the NLRP3 inflammasome. Eur J Immunol 43(3), 679-692.
Cheng SC, Sprong T, Joosten LA, van der Meer JW, Kullberg BJ, Hube B, Schejbel L, Garred P, van Deuren M, Netea MG (2012) Complement plays a central role in Candida albicans-induced cytokine production by human PBMCs. Eur J Immunol 42(4), 993-991004.
Seider K, Brunke S, Schild L, Jablonowski N, Wilson D, Majer O, Barz D, Haas A, Kuchler K, Schaller M, Hube B (2011) The facultative intracellular pathogen Candida glabrata subverts macrophage cytokine production and phagolysosome maturation. J Immunol 187(6), 3072-3086.
Brunke S, Seider K, Almeida RS, Heyken A, Fleck CB, Brock M, Barz D, Rupp S, Hube B (2010) Candida glabrata tryptophan-based pigment production via the Ehrlich pathway. Mol Microbiol 76(1), 25-47.

Funding