Interaktion mit Immunzellen

Phagozyten wie Makrophagen und Neutrophile sind zentrale Komponenten des angeborenen Immunsystems und stellen damit die erste Abwehrlinie gegen pathogene Candida-Spezies wie C. albicans und C. glabrata dar. Die Erkennung von Candida-Zellen durch Phagozyten führt zur Freisetzung von Zytokinen, zur Phagozytose sowie zur Aktivierung von antimikrobiellen Effektorfunktionen, die zum Abtöten des Pilzes führen sollen.

Pathogene Candida spp. sind jedoch sehr gut an ihren Wirt angepasst und haben Mechanismen entwickelt, um den antimikrobiellen Aktivitäten von Phagozyten zu entkommen oder entgegenzuwirken.

Beide Pilze können zum Beispiel die Phagozytose durch Makrophagen überleben und sogar intrazellulär wachsen und ausbrechen.

Wir wollen die Interaktion von C. albicans und C. glabrata mit Phagozyten charakterisieren. Dabei sind wir besonders an den Pilzfaktoren und -aktivitäten interessiert, die Candida das Überleben in diesen Immunzellen ermöglichen.

Publikationen

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

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

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

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

Mitarbeiter

Stefanie Allert

Telefon: +49 3641 532-1141 E-Mail: stefanie.allert@leibniz-hki.de

Dr. Lydia Kasper

Telefon: +49 3641 532-1219 E-Mail: lydia.kasper@leibniz-hki.de

Annika König

Marcel Sprenger

Telefon: +49 3641 532-1346 E-Mail: marcel.sprenger@leibniz-hki.de