Τίτλος:
Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Συγγραφείς:
Bruno, M.
Kersten, S.
Bain, J.M.
Jaeger, M.
Rosati, D.
Kruppa, M.D.
Lowman, D.W.
Rice, P.J.
Graves, B.
Ma, Z.
Jiao, Y.N.
Chowdhary, A.
Renieris, G.
van de Veerdonk, F.L.
Kullberg, B.-J.
Giamarellos-Bourboulis, E.J.
Hoischen, A.
Gow, N.A.R.
Brown, A.J.P.
Meis, J.F.
Williams, D.L.
Netea, M.G.
Περιοδικό:
Nature Microbiology
Εκδότης:
Institute of Geographic Sciences and Natural Resources Research
Λέξεις-κλειδιά:
interleukin 1 receptor blocking agent; interleukin 1beta; interleukin 6; lectin receptor; mannoprotein; transcriptome; tumor necrosis factor; cytokine; lectin, adult; animal experiment; animal model; animal tissue; Article; Candida albicans; Candida auris; cell function; controlled study; cytokine production; cytokine response; cytolysis; female; fungal virulence; genetic transcription; human; human cell; immune response; immunocompetent cell; in vivo study; infant; innate immunity; invasive candidiasis; macrophage; male; mononuclear cell; mouse; nonhuman; priority journal; animal; C57BL mouse; Candida; candidiasis; genetic transcription; genetics; immunity; immunology; microbiology; pathogenicity; physiology; virulence, Animals; Candida; Candidiasis; Cytokines; Humans; Immunity; Lectins, C-Type; Male; Mice; Mice, Inbred C57BL; Transcription, Genetic; Virulence
DOI:
10.1038/s41564-020-0780-3
