Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells

Rieber N, Singh A, Oez H, Carevic M, Bouzani M, Amich J, Ost M, Ye Z, Ballbach M, Schaefer I, Mezger M, Klimosch SN, Weber ANR, Handgretinger R, Krappmann S, Liese J, Engeholm M, Schuele R, Salih HR, Marodi L, Speckmann C, Grimbacher B, Ruland J, Brown GD, Beilhack A, Loeffler J, Hartl D (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Cell Host & Microbe Elsevier (Cell Press)

Book Volume: 17

Pages Range: 507-14

Journal Issue: 4

DOI: 10.1016/j.chom.2015.02.007

Abstract

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-1? 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.

Authors with CRIS profile

Sven Krappmann Professur für Klinische Mikrobiologie und Immunologie

Involved external institutions

Eberhard Karls Universität Tübingen DE Germany (DE) Julius-Maximilians-Universität Würzburg DE Germany (DE) Universitätsklinikum Würzburg DE Germany (DE) University of Aberdeen GB United Kingdom (GB) Technische Universität München (TUM) DE Germany (DE) Universitätsklinikum Freiburg DE Germany (DE) University of Debrecen / Debreceni Egyetem HU Hungary (HU)

How to cite

APA:

Rieber, N., Singh, A., Oez, H., Carevic, M., Bouzani, M., Amich, J.,... Hartl, D. (2015). Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells. Cell Host & Microbe, 17(4), 507-14. https://doi.org/10.1016/j.chom.2015.02.007

MLA:

Rieber, Nikolaus, et al. "Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells." Cell Host & Microbe 17.4 (2015): 507-14.

BibTeX: Download