Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris.


Journal

Nature microbiology
ISSN: 2058-5276
Titre abrégé: Nat Microbiol
Pays: England
ID NLM: 101674869

Informations de publication

Date de publication:
12 2020
Historique:
received: 10 07 2019
accepted: 27 07 2020
pubmed: 26 8 2020
medline: 27 2 2021
entrez: 26 8 2020
Statut: ppublish

Résumé

Candida auris is among the most important emerging fungal pathogens, yet mechanistic insights into its immune recognition and control are lacking. Here, we integrate transcriptional and functional immune-cell profiling to uncover innate defence mechanisms against C. auris. C. auris induces a specific transcriptome in human mononuclear cells, a stronger cytokine response compared with Candida albicans, but a lower macrophage lysis capacity. C. auris-induced innate immune activation is mediated through the recognition of C-type lectin receptors, mainly elicited by structurally unique C. auris mannoproteins. In in vivo experimental models of disseminated candidiasis, C. auris was less virulent than C. albicans. Collectively, these results demonstrate that C. auris is a strong inducer of innate host defence, and identify possible targets for adjuvant immunotherapy.

Identifiants

pubmed: 32839538
doi: 10.1038/s41564-020-0780-3
pii: 10.1038/s41564-020-0780-3
pmc: PMC9204844
mid: NIHMS1810177
doi:

Substances chimiques

Cytokines 0
Lectins, C-Type 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1516-1531

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM083016
Pays : United States
Organisme : Medical Research Council
ID : MR/M026663/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M026663/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N006364/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N006364/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NCRR NIH HHS
ID : C06 RR030651
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM119197
Pays : United States

Commentaires et corrections

Type : CommentIn

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Auteurs

Mariolina Bruno (M)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. Mariolina.Bruno@radboudumc.nl.

Simone Kersten (S)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Judith M Bain (JM)

Medical Research Council Centre for Medical Mycology, University of Aberdeen, Aberdeen, UK.

Martin Jaeger (M)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Diletta Rosati (D)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Michael D Kruppa (MD)

Departments of Surgery, Biomedical Sciences and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Douglas W Lowman (DW)

Departments of Surgery, Biomedical Sciences and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Peter J Rice (PJ)

Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.

Bridget Graves (B)

Departments of Surgery, Biomedical Sciences and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Zuchao Ma (Z)

Departments of Surgery, Biomedical Sciences and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Yue Ning Jiao (YN)

Departments of Surgery, Biomedical Sciences and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Anuradha Chowdhary (A)

Department of Medical Mycology, Vallabhbhai Patel Chest Institute, University of Delhi, New Delhi, India.

George Renieris (G)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Frank L van de Veerdonk (FL)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Center of Expertise in Mycology, Radboud University Medical Center and Canisius Wilhelmina Hospital, Nijmegen, the Netherlands.

Bart-Jan Kullberg (BJ)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Center of Expertise in Mycology, Radboud University Medical Center and Canisius Wilhelmina Hospital, Nijmegen, the Netherlands.

Evangelos J Giamarellos-Bourboulis (EJ)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Alexander Hoischen (A)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Human Genetics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

Neil A R Gow (NAR)

Medical Research Council Centre for Medical Mycology, University of Aberdeen, Aberdeen, UK.
MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.

Alistair J P Brown (AJP)

Medical Research Council Centre for Medical Mycology, University of Aberdeen, Aberdeen, UK.
MRC Centre for Medical Mycology, University of Exeter, Exeter, UK.

Jacques F Meis (JF)

Center of Expertise in Mycology, Radboud University Medical Center and Canisius Wilhelmina Hospital, Nijmegen, the Netherlands.
Bioprocess Engineering and Biotechnology Graduate Program, Federal University of Paraná, Curitiba, Brazil.
Department of Medical Microbiology and Infectious Diseases, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands.

David L Williams (DL)

Departments of Surgery, Biomedical Sciences and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.

Mihai G Netea (MG)

Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands. mihai.netea@radboudumc.nl.
Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany. mihai.netea@radboudumc.nl.

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