Differential Regulation of Myeloid-Derived Suppressor Cells by Candida Species.

Anurag Singh,Stefanie Braig,Felipe Lelis,Iris Schäfer,Nikolaus Rieber,Dominik Hartl

doi:10.3389/fmicb.2016.01624

Abstract

Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their ability to suppress T-cell responses. Recently, we demonstrated that the human-pathogenic fungi Candida albicans and Aspergillus fumigatus induced a distinct subset of neutrophilic MDSCs. To dissect Candida-mediated MDSC induction in more depth, we studied the relative efficacy of different pathogenic non-albicans Candida species to induce and functionally modulate neutrophilic MDSCs, including C. glabrata, C. parapsilosis, C. dubliniensis, and C. krusei. Our data demonstrate that the extent of MDSC generation is largely dependent on the Candida species with MDSCs induced by C. krusei and C. glabrata showing a higher suppressive activity compared to MDSCs induced by C. albicans. In summary, these studies show that fungal MDSC induction is differentially regulated at the species level and differentially affects effector T-cell responses.

Highlights

Candida species cause one of the most prevalent fungal infections worldwide (Pfaller and Diekema, 2007; Brown et al, 2012)
To further broaden our understanding of how Myeloid-derived suppressor cells (MDSCs) play a role in modulating the host immune response to Candida infections, we studied the relative efficacy of different pathogenic Non-albicans Candida (NAC) species to induce neutrophilic MDSCs, including C. glabrata, C. krusei, C. parapsilosis, and C. dubliniensis
Isolated human Peripheral blood mononuclear cells (PBMCs) were cultured in well flat-bottom plates (Corning) or cm2 flasks (Greiner Bio-One) at 5 × 105 cells/ml in RPMI 1640 supplemented with 10% heat-inactivated FCS (PAA Laboratories), 2 mM glutamine (Sigma-Aldrich), 100 IU/ml penicillin, and 100 mg/ml streptomycin (Biochrom; referred to as “complete medium”) for 6 days, and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (10 ng/ml, Genzyme), heat-inactivated C. albicans, C. glabrata, C. krusei, C. dubliniensis, and C. parapsilosis were added at a ratio of 1:5 (Fungi:PBMC) as indicated in figures

Summary

Introduction

Candida species cause one of the most prevalent fungal infections worldwide (Pfaller and Diekema, 2007; Brown et al, 2012). The genus Candida consists of multiple species that show a considerable variation in terms of their virulence and phenotype and recent studies showed that diseases caused by NAC species are on the rise (Merseguel et al, 2015). While C. albicans is well characterized in terms of recognition through PRRs mainly CLRs like Dectin-1, Dectin-2, mannose receptor (MR) and Mincle (Brown, 2010; Plato et al, 2015), recognition of NAC species is less precisely defined. In contrast to C. albicans, phagocytosis of C. parapsilosis by neutrophils was not impaired following Dectin-1 blockade in vitro (Linden et al, 2010) and, dectin-1−/− bone marrow macrophages showed no defect in binding to C. glabrata (Kuhn and Vyas, 2012). Studies indicated that Dectin-2 played a more important role in C. glabrata infection than Dectin-1 (Ifrim et al, 2014)

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Conclusion