In Vitro Infection Models to Study Fungal-host Interactions

Overview

Journal FEMS Microbiol Rev

Publisher Oxford University Press

Specialty Microbiology

Date 2021 Feb 1

PMID 33524102

Citations 13

Authors

Antonia Last

Michelle Maurer

Alexander S Mosig

Mark S Gresnigt

Bernhard Hube

Affiliations

Soon will be listed here.

Abstract

Fungal infections (mycoses) affect over a billion people per year. Approximately, two million of these infections are life-threatening, especially for patients with a compromised immune system. Fungi of the genera Aspergillus, Candida, Histoplasma and Cryptococcus are opportunistic pathogens that contribute to a substantial number of mycoses. To optimize the diagnosis and treatment of mycoses, we need to understand the complex fungal-host interplay during pathogenesis, the fungal attributes causing virulence and how the host resists infection via immunological defenses. In vitro models can be used to mimic fungal infections of various tissues and organs and the corresponding immune responses at near-physiological conditions. Furthermore, models can include fungal interactions with the host-microbiota to mimic the in vivo situation on skin and mucosal surfaces. This article reviews currently used in vitro models of fungal infections ranging from cell monolayers to microfluidic 3D organ-on-chip (OOC) platforms. We also discuss how OOC models can expand the toolbox for investigating interactions of fungi and their human hosts in the future.

Citing Articles

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References

Long K, Gomez F, Morris R, Newman S . Identification of heat shock protein 60 as the ligand on Histoplasma capsulatum that mediates binding to CD18 receptors on human macrophages. J Immunol. 2002; 170(1):487-94. DOI: 10.4049/jimmunol.170.1.487. View

Meir J, Hartmann E, Eckstein M, Guiducci E, Kirchner F, Rosenwald A . Identification of Candida albicans regulatory genes governing mucosal infection. Cell Microbiol. 2018; 20(8):e12841. DOI: 10.1111/cmi.12841. View

Schaller M, Schafer W, Korting H, Hube B . Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity. Mol Microbiol. 1998; 29(2):605-15. DOI: 10.1046/j.1365-2958.1998.00957.x. View

Raasch M, Rennert K, Jahn T, Gartner C, Schonfelder G, Huber O . An integrative microfluidically supported in vitro model of an endothelial barrier combined with cortical spheroids simulates effects of neuroinflammation in neocortex development. Biomicrofluidics. 2016; 10(4):044102. PMC: 4947035. DOI: 10.1063/1.4955184. View

Thak E, Lee S, Xu-Vanpala S, Lee D, Chung S, Bahn Y . Core -Glycan Structures Are Critical for the Pathogenicity of Cryptococcus neoformans by Modulating Host Cell Death. mBio. 2020; 11(3). PMC: 7218283. DOI: 10.1128/mBio.00711-20. View

Wellington M, Dolan K, Krysan D . Live Candida albicans suppresses production of reactive oxygen species in phagocytes. Infect Immun. 2008; 77(1):405-13. PMC: 2612242. DOI: 10.1128/IAI.00860-08. View

van der Does A, Joosten S, Vroomans E, Bogaards S, van Meijgaarden K, Ottenhoff T . The antimicrobial peptide hLF1-11 drives monocyte-dendritic cell differentiation toward dendritic cells that promote antifungal responses and enhance Th17 polarization. J Innate Immun. 2012; 4(3):284-92. PMC: 6741610. DOI: 10.1159/000332941. View

Kumar R, Saraswat D, Tati S, Edgerton M . Novel Aggregation Properties of Candida albicans Secreted Aspartyl Proteinase Sap6 Mediate Virulence in Oral Candidiasis. Infect Immun. 2015; 83(7):2614-26. PMC: 4468525. DOI: 10.1128/IAI.00282-15. View

Aimanianda V, Bayry J, Bozza S, Kniemeyer O, Perruccio K, Elluru S . Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature. 2009; 460(7259):1117-21. DOI: 10.1038/nature08264. View

10.

Coady A, Sil A . MyD88-dependent signaling drives host survival and early cytokine production during Histoplasma capsulatum infection. Infect Immun. 2015; 83(4):1265-75. PMC: 4363404. DOI: 10.1128/IAI.02619-14. View

11.

Voelz K, May R . Cryptococcal interactions with the host immune system. Eukaryot Cell. 2010; 9(6):835-46. PMC: 2901644. DOI: 10.1128/EC.00039-10. View

12.

Morton C, Wurster S, Fliesser M, Ebel F, Page L, Hunniger K . Validation of a simplified in vitro Transwell model of the alveolar surface to assess host immunity induced by different morphotypes of Aspergillus fumigatus. Int J Med Microbiol. 2018; 308(8):1009-1017. DOI: 10.1016/j.ijmm.2018.09.001. View

13.

Lewis L, Bain J, Lowes C, Gillespie C, Rudkin F, Gow N . Stage specific assessment of Candida albicans phagocytosis by macrophages identifies cell wall composition and morphogenesis as key determinants. PLoS Pathog. 2012; 8(3):e1002578. PMC: 3305454. DOI: 10.1371/journal.ppat.1002578. View

14.

Kunyeit L, Kurrey N, Anu-Appaiah K, Rao R . Probiotic Yeasts Inhibit Virulence of Non Species. mBio. 2019; 10(5). PMC: 6794482. DOI: 10.1128/mBio.02307-19. View

15.

Van Prooyen N, Henderson C, Hocking Murray D, Sil A . CD103+ Conventional Dendritic Cells Are Critical for TLR7/9-Dependent Host Defense against Histoplasma capsulatum, an Endemic Fungal Pathogen of Humans. PLoS Pathog. 2016; 12(7):e1005749. PMC: 4961300. DOI: 10.1371/journal.ppat.1005749. View

16.

Vallabhaneni S, Chiller T . Fungal Infections and New Biologic Therapies. Curr Rheumatol Rep. 2016; 18(5):29. DOI: 10.1007/s11926-016-0572-1. View

17.

Nayak D, Mendez O, Bowen S, Mohanakumar T . Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages. J Vis Exp. 2018; (134). PMC: 6100701. DOI: 10.3791/57287. View

18.

Becker K, Aimanianda V, Wang X, Gresnigt M, Ammerdorffer A, Jacobs C . Aspergillus Cell Wall Chitin Induces Anti- and Proinflammatory Cytokines in Human PBMCs via the Fc-γ Receptor/Syk/PI3K Pathway. mBio. 2016; 7(3). PMC: 4895119. DOI: 10.1128/mBio.01823-15. View

19.

Casaroto A, Silva R, Salmeron S, de Rezende M, Dionisio T, Dos Santos C . -Cell Interactions Activate Innate Immune Defense in Human Palate Epithelial Primary Cells via Nitric Oxide (NO) and β-Defensin 2 (hBD-2). Cells. 2019; 8(7). PMC: 6678605. DOI: 10.3390/cells8070707. View

20.

Weiss E, Ziegler S, Fliesser M, Schmitt A, Hunniger K, Kurzai O . First Insights in NK-DC Cross-Talk and the Importance of Soluble Factors During Infection With . Front Cell Infect Microbiol. 2018; 8:288. PMC: 6110135. DOI: 10.3389/fcimb.2018.00288. View