Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways

Mariolina Bruno; Intan M W Dewi; Vicky Matzaraki; Rob Ter Horst; Marina Pekmezovic; Berenice Rösler; Laszlo Groh; Rutger J Röring; Vinod Kumar; Yang Li; Agostinho Carvalho; Mihai G Netea; Jean-Paul Latgé; Mark S Gresnigt; Frank L van de Veerdonk

doi:10.1016/j.csbj.2020.12.036

Comparative host transcriptome in response to pathogenic fungi identifies common and species-specific transcriptional antifungal host response pathways

Comput Struct Biotechnol J. 2020 Dec 26:19:647-663. doi: 10.1016/j.csbj.2020.12.036. eCollection 2021.

Authors

Mariolina Bruno¹, Intan M W Dewi¹, Vicky Matzaraki¹, Rob Ter Horst¹, Marina Pekmezovic², Berenice Rösler¹, Laszlo Groh¹, Rutger J Röring¹, Vinod Kumar^{1

3}, Yang Li^{1

4

5}, Agostinho Carvalho^{6

7}, Mihai G Netea^{1

8}, Jean-Paul Latgé⁹, Mark S Gresnigt^{1

10}, Frank L van de Veerdonk¹

Affiliations

¹ Department of Internal Medicine and Radboudumc Center for Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
² Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11a 07745, Jena, Germany.
³ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁴ Centre for Individualised Infection Medicine (CiiM) and TWINCORE, Joint Ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
⁵ Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
⁶ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
⁷ ICVS/3B's - PT Government Associate Laboratory, Guimarães/Braga, Portugal.
⁸ Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany.
⁹ Unité des Aspergillus, Institut Pasteur, Paris, France.
¹⁰ Junior Research Group Adaptive Pathogenicity Strategies, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knöll Institute, Beutenbergstraße 11a 07745, Jena, Germany.

Abstract

Candidiasis, aspergillosis, and mucormycosis cause the majority of nosocomial fungal infections in immunocompromised patients. Using an unbiased transcriptional profiling in PBMCs exposed to the fungal species causing these infections, we found a core host response in healthy individuals that may govern effective fungal clearance: it consists of 156 transcripts, involving canonical and non-canonical immune pathways. Systematic investigation of key steps in antifungal host defense revealed fungal-specific signatures. As previously demonstrated, Candida albicans induced type I and Type II interferon-related pathways. In contrast, central pattern recognition receptor, reactive oxygen species production, and host glycolytic pathways were down-regulated in response to Rhizopus oryzae, which was associated with an ER-stress response. TLR5 was identified to be uniquely regulated by Aspergillus fumigatus and to control cytokine release in response to this fungus. In conclusion, our data reveals the transcriptional profiles induced by C. albicans, A. fumigatus, and R. oryzae, and describes both the common and specific antifungal host responses that could be exploited for novel therapeutic strategies.

Keywords: A. fumigatus; Antifungal core host response; C. albicans; Cytokines; Host immune response; Immunometabolism; Opportunistic infections; Pattern recognition receptors; R. oryzae; RNAseq; Transcriptomics of pathogenic fungi.