Interaction with immune cells

Phagocytes such as macrophages and neutrophils are key players of the innate immune system and thus constitute the first line of defense against pathogenic Candida species such as C. albicans and C. glabrata. 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. Both fungi are, for example, able to not only survive phagocytosis by macrophages, but even proliferate intracellularly and escape.

We want to characterize the interaction of C. albicans and C. glabrata with phagocytes. We are especially interested in the fungal factors and activities that help Candida to cope with these immune cells and survive.

Publications

Bacher P, Hohnstein T, Beerbaum E, Röcker M, Blango MG, Kaufmann S, Röhmel J, Eschenhagen P, Grehn C, Seidel K, Rickerts V, Lozza L, Stervbo U, Nienen M, Babel N, Milleck J, Assenmacher M, Cornely OA, Ziegler M, Wisplinghoff H, Heine G, Worm M, Siegmund B, Maul J, Creutz P, Tabeling C, Ruwwe-Glösenkamp C, Sander LE, Knosalla C, Brunke S, Hube B, Kniemeyer O, Brakhage AA, Schwarz C, Scheffold A (2019) Human anti-fungal Th17 immunity and pathology rely on cross-reactivity against Candida albicans. Cell 176(6), 1340-1355.e15. Details PubMed

Domínguez-Andrés J, Novakovic B, Li Y, Scicluna BP, Gresnigt MS, Arts RJW, Oosting M, Moorlag SJCFM, Groh LA, Zwaag J, Koch RM, Ter Horst R, Joosten LAB, Wijmenga C, Michelucci A, van der Poll T, Kox M, Pickkers P, Kumar V, Stunnenberg H, Netea MG (2019) The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell Metab [Accepted] Details PubMed

Drummond RA, Swamydas M, Oikonomou V, Zhai B, Dambuza IM, Schaefer BC, Bohrer AC, Mayer-Barber KD, Lira SA, Iwakura Y, Filler SG, Brown GD, Hube B, Naglik JR, Hohl TM, Lionakis MS (2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570. Details PubMed

Fischer D, Gessner G, Fill TP, Barnett R, Tron K, Dornblut K, Kloss F, Stallforth P, Hube B, Heinemann SH, Hertweck C, Scherlach K, Brunke S (2019) Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother [Accepted] Details PubMed

Gabaldón T (2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev , Details PubMed

Grondman I, Arts RJW, Koch RM, Leijte GP, Gerretsen J, Bruse N, Kempkes RWM, Ter Horst R, Kox M, Pickkers P, Netea MG, Gresnigt MS (2019) Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst. J Leukoc Biol [Accepted] Details PubMed

Ho J, Yang X, Nikou SA, Kichik N, Donkin A, Ponde NO, Richardson JP, Gratacap RL, Archambault LS, Zwirner CP, Murciano C, Henley-Smith R, Thavaraj S, Tynan CJ, Gaffen SL, Hube B, Wheeler RT, Moyes DL, Naglik JR (2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297. Details PubMed

Jaeger M, Matzaraki V, Aguirre-Gamboa R, Gresnigt MS, Chu X, Johnson MD, Oosting M, Smeekens SP, Withoff S, Jonkers I, Perfect JR, van de Veerdonk FL, Kullberg BJ, Joosten LAB, Li Y, Wijmenga C, Netea MG, Kumar V (2019) A Genome-Wide Functional Genomics Approach Identifies Susceptibility Pathways to Fungal Bloodstream Infection in Humans. J Infect Dis [Accepted] Details PubMed

Jaeger M, Pinelli M, Borghi M, Constantini C, Dindo M, van Emst L, Puccetti M, Pariano M, Ricaño-Ponce I, Büll C, Gresnigt MS, Wang X, Gutierrez Achury J, Jacobs CWM, Xu N, Oosting M, Arts P, Joosten LAB, van de Veerdonk FL, Veltman JA, Ten Oever J, Kullberg BJ, Feng M, Adema GJ, Wijmenga C, Kumar V, Sobel J, Gilissen C, Romani L, Netea MG (2019) A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis. Sci Transl Med [Accepted] Details PubMed

Naglik JR, Gaffen SL, Hube B (2019) Candidalysin: discovery and function in Candida albicans infections. Curr Opin Microbiol [Accepted] Details PubMed

Swidergall M, Khalaji M, Solis N, Moyes D, Drummond R, Hube B, Lionakis M, Murdoch C, Filler S, Naglik J (2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection Journal of Infectious Diseases [Accepted] Details

Westman J, Hube B, Fairn GD (2019) Integrity under stress: Host membrane remodelling and damage by fungal pathogens. Cell Microbiol 21(4), e13016. Details PubMed Open Access

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 [Accepted] Details PubMed

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. Details PubMed

Verma AH, Richardson JP, Zhou C, Coleman BM, Moyes DL, Ho J, Huppler AR, Ramani K, McGeachy MJ, Mufazalov IA, Waisman A, Kane LP, Biswas PS, Hube B, Naglik JR, Gaffen SL (2017) Oral epithelial cells orchestrate innate type 17 responses to Candida albicans through the virulence factor candidalysin. Sci Immunol 2(17), pii: eaam8834. Details PubMed

Cassone A, Vecchiarelli A, Hube B (2016) Aspartyl proteinases of eukaryotic microbial pathogens: From eating to heating. PLOS Pathog 12(12), e1005992. (Review) Details PubMed Open Access

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. Details PubMed Open Access

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. Details PubMed Open Access

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. Details PubMed

Kasper L, Seider K, Hube B (2015) Intracellular survival of Candida glabrata in macrophages: immune evasion and persistence. FEMS Yeast Res 15(5), fov042. Details PubMed

Pericolini E, Gabrielli E, Amacker M, Kasper L, Roselletti E, Luciano E, Sabbatini S, Kaeser M, Moser C, Hube B, Vecchiarelli A, Cassone A (2015) Secretory aspartyl proteinases cause vaginitis and can mediate vaginitis caused by Candida albicans in mice. MBio 6(3), e00724. Details PubMed Open Access PDF

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. Details PubMed Open Access

Hebecker B, Naglik JR, Hube B, Jacobsen ID (2014) Pathogenicity mechanisms and host response during oral Candida albicans infections. Expert Rev Anti Infect Ther 12(7), 867-879. (Review) Details PubMed

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. Details PubMed Open Access

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. Details PubMed

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. Details PubMed

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. Details PubMed

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. Details PubMed

Martin R, Albrecht-Eckardt D, Brunke S, Hube B, Hünniger K, Kurzai O (2013) A core filamentation response network in Candida albicans is restricted to eight genes. PLOS One 8(3), e58613. Details PubMed Open Access

Mayer FL, Wilson D, Hube B (2013) Hsp21 potentiates antifungal drug tolerance in Candida albicans. PLOS One 8(3), e60417. Details PubMed

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) Details PubMed

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. Details PubMed

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. Details PubMed

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. Details PubMed

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. Details PubMed

Jacobsen ID, Brunke S, Seider K, Schwarzmüller T, Firon A, d'Enfért C, Kuchler K, Hube B (2010) Candida glabrata persistence in mice does not depend on host immunosuppression and is unaffected by fungal amino acid auxotrophy. Infect Immun 78(3), 1066-1077. Details PubMed

Seider K, Heyken A, Lüttich A, Miramón P, Hube B (2010) Interaction of pathogenic yeasts with phagocytes: survival, persistence and escape. Curr Opin Microbiol 13(4), 392-400. (Review) Details PubMed

Staff

Dr. Stefanie Allert

Phone: +49 3641 532-1141 Email: stefanie.allert@leibniz-hki.de

Dr. Lydia Kasper

Phone: +49 3641 532-1219 Email: lydia.kasper@leibniz-hki.de

Annika König

Marcel Sprenger

Phone: +49 3641 532-1346 Email: marcel.sprenger@leibniz-hki.de