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

Nikolaus Rieber1, Anurag Singh1, Hasan Öz1

  • 1Department of Pediatrics I, University of Tübingen, 72076 Tübingen, Germany.

Cell Host & Microbe
|March 17, 2015
PubMed

Insights

Pathogenic fungi induce specific myeloid-derived suppressor cells (MDSCs) to control T and NK cell responses. These MDSCs protect against Candida albicans but not Aspergillus fumigatus infection, revealing a key innate immune regulation mechanism.

Area of Science:

  • Immunology
  • Mycology
  • Infectious Diseases

Background:

  • Immunocompetent individuals rarely mount pro-inflammatory antifungal immune responses despite constant fungal exposure.
  • The mechanisms underlying this immune tolerance are not fully understood.

Purpose of the Study:

  • To investigate the role of myeloid-derived suppressor cells (MDSCs) in regulating host defense against fungal infections.
  • To elucidate the molecular pathways involved in fungal-induced MDSC generation.

Main Methods:

  • Utilized mouse models and human patient samples.
  • Investigated the role of Dectin-1, CARD9, reactive oxygen species (ROS), caspase-8, and interleukin-1 (IL-1) in fungal-induced MDSC production.
  • Performed adoptive transfer and survival experiments.

Main Results:

  • Fungal infections with Aspergillus fumigatus and Candida albicans induce a specific subset of neutrophilic MDSCs.
  • These MDSCs suppress T and NK cell responses via Dectin-1, CARD9, ROS, caspase-8, and IL-1 signaling.
  • MDSCs conferred protection during invasive C. albicans infection but not A. fumigatus infection.

Conclusions:

  • Pathogenic fungi employ MDSCs as an innate immune mechanism to modulate host defense.
  • The findings highlight a novel tolerogenic pathway crucial for managing fungal infections.
  • Differential protective roles of MDSCs against distinct fungal pathogens were observed.

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