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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells
Cell Host and Microbe, Volume 17, No. 4, Year 2015
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Description
Despite continuous contact with fungi, immunocompetent individuals rarely develop pro-inflammatory antifungal immune responses. The underlying tolerogenic mechanisms are incompletely understood. Using both mouse models and human patients, we show that infection with the human pathogenic fungi Aspergillus fumigatus and Candida albicans induces a distinct subset of neutrophilic myeloid-derived suppressor cells (MDSCs), which functionally suppress T and NK cell responses. Mechanistically, pathogenic fungi induce neutrophilic MDSCs through the pattern recognition receptor Dectin-1 and its downstream adaptor protein CARD9. Fungal MDSC induction is further dependent on pathways downstream of Dectin-1 signaling, notably reactive oxygen species (ROS) generation as well as caspase-8 activity and interleukin-1 (IL-1) production. Additionally, exogenous IL-1β induces MDSCs to comparable levels observed during C. albicans infection. Adoptive transfer and survival experiments show that MDSCs are protective during invasive C. albicans infection, but not A. fumigatus infection. These studies define an innate immune mechanism by which pathogenic fungi regulate host defense. © 2015 The Authors.
Authors & Co-Authors
Rieber, Nikolaus
Germany, Tubingen
Eberhard Karls Universität Tübingen
Singh, Anurag
Germany, Tubingen
Eberhard Karls Universität Tübingen
Klimosch, Sascha N.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Weber, Alexander N.R.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Handgretinger, Rupert J.
Germany, Tubingen
Eberhard Karls Universität Tübingen
Liese, Johannes Günter M.
Germany, Wurzburg
Julius-maximilians-universität Würzburg
Schüle, Rebecca
Germany, Tubingen
Eberhard Karls Universität Tübingen
Máródi, László D.R.
Hungary, Debrecen
Debreceni Egyetem
Speckmann, Carsten
Germany, Freiburg Im Breisgau
Universität Freiburg
Grimbacher, Bodo
Germany, Freiburg Im Breisgau
Universität Freiburg
Ruland, Jürgen
Germany, Munich
Tum Fakultät Für Medizin
Brown, Gordon D.A.
United Kingdom, Aberdeen
University of Aberdeen
Beilhack, Andreas
Unknown Affiliation
Hartl, Dominik
Germany, Tubingen
Eberhard Karls Universität Tübingen
Statistics
Citations: 90
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1016/j.chom.2015.02.007
ISSN:
19313128