Oncotarget

Research Papers:

Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus

Stanislaw Schmidt, Lars Tramsen, Andreas Schneider, Ralf Schubert, Ada Balan, Özer Degistirici, Roland Meisel and Thomas Lehrnbecher _

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Oncotarget. 2017; 8:95495-95503. https://doi.org/10.18632/oncotarget.20753

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Abstract

Stanislaw Schmidt1, Lars Tramsen1, Andreas Schneider1, Ralf Schubert2, Ada Balan1,3, Özer Degistirici4, Roland Meisel4 and Thomas Lehrnbecher1

1Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany

2Divisions for Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany

3Division for “Victor Babes”, University of Medicine and Pharmacy, Timisoara, Romania

4Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

Correspondence to:

Thomas Lehrnbecher, email: Thomas.Lehrnbecher@kgu.de

Keywords: mesenchymal stromal cells; Aspergillus fumigatus; phagocytosis; hematopoietic stem cell transplantation; immunotherapy

Received: June 09, 2017     Accepted: August 03, 2017     Published: September 08, 2017

ABSTRACT

Mesenchymal stromal cells (MSCs) are increasingly given as immunotherapy to hematopoietic stem cell transplant (HSCT) recipients with refractory graft-versus-host disease (GvHD). Whereas the immunosuppressive properties of MSCs seem to be beneficial in GvHD, there is, at the same time, major concern that MSCs increase the risk for infection. We therefore investigated the interplay of human MSCs with Aspergillus fumigatus and the impact of MSCs on different arms of the anti-Aspergillus host response in vitro. Although A. fumigatus hyphae increase mRNA levels of IL6 in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte Aspergillus conidia, but phagocytosis of conidia is not associated with an alteration of the cytokine production by MSCs. In addition, human MSCs do not affect activation and function of A. fumigatus specific CD4+ T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our in vitro data indicate that administration of human MSCs is not associated with a negative impact on the host response against A. fumigatus and that the fungus does not stimulate MSCs to increase the release of those cytokines which play a central role in the pathophysiology of GvHD.


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