Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus
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...
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Published in | Oncotarget Vol. 8; no. 56; pp. 95495 - 95503 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Impact Journals LLC
10.11.2017
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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
and the impact of MSCs on different arms of the anti-
host response
. Although
hyphae increase mRNA levels of
in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte
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
specific CD4
T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our
data indicate that administration of human MSCs is not associated with a negative impact on the host response against
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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AbstractList | 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. 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 and the impact of MSCs on different arms of the anti- host response . Although hyphae increase mRNA levels of in MSCs, the extracellular availability of IL-6 and other pro-inflammatory cytokines remains unaffected. Human MSCs are able to phagocyte 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 specific CD4 T cells, and MSCs do not negatively impact the oxidative burst activity of phagocytes. Our data indicate that administration of human MSCs is not associated with a negative impact on the host response against 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. 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. |
Author | Degistirici, Özer Lehrnbecher, Thomas Schneider, Andreas Meisel, Roland Schmidt, Stanislaw Schubert, Ralf Tramsen, Lars Balan, Ada |
AuthorAffiliation | 1 Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany 4 Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany 3 Division for “Victor Babes”, University of Medicine and Pharmacy, Timisoara, Romania 2 Divisions for Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany |
AuthorAffiliation_xml | – name: 4 Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany – name: 1 Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany – name: 3 Division for “Victor Babes”, University of Medicine and Pharmacy, Timisoara, Romania – name: 2 Divisions for Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany |
Author_xml | – sequence: 1 givenname: Stanislaw surname: Schmidt fullname: Schmidt, Stanislaw organization: Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany – sequence: 2 givenname: Lars surname: Tramsen fullname: Tramsen, Lars organization: Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany – sequence: 3 givenname: Andreas surname: Schneider fullname: Schneider, Andreas organization: Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany – sequence: 4 givenname: Ralf surname: Schubert fullname: Schubert, Ralf organization: Divisions for Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany – sequence: 5 givenname: Ada surname: Balan fullname: Balan, Ada organization: Division for "Victor Babes", University of Medicine and Pharmacy, Timisoara, Romania – sequence: 6 givenname: Özer surname: Degistirici fullname: Degistirici, Özer organization: Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany – sequence: 7 givenname: Roland surname: Meisel fullname: Meisel, Roland organization: Division of Pediatric Stem Cell Therapy, Clinic for Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany – sequence: 8 givenname: Thomas surname: Lehrnbecher fullname: Lehrnbecher, Thomas organization: Divisions for Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany |
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Cites_doi | 10.1038/cr.2012.179 10.1007/s12015-014-9495-2 10.1086/519389 10.1038/leu.2014.127 10.1186/scrt537 10.1111/j.1462-5822.2011.01605.x 10.1093/infdis/166.3.580 10.1038/nri2939 10.1111/j.1365-2141.2004.04922.x 10.1093/infdis/jiq062 10.1093/infdis/jit574 10.1182/blood-2005-04-1660 10.1182/blood-2003-02-0456 10.1158/1078-0432.CCR-10-1198 10.1182/blood-2005-05-1775 10.1097/01.TP.0000082540.43730.80 10.1093/mmy/myv110 10.1111/myc.12241 10.1006/meth.2001.1262 10.1016/j.bbmt.2011.09.003 10.18632/oncotarget.12616 10.1038/leu.2011.108 10.1186/scrt216 |
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Keywords | hematopoietic stem cell transplantation phagocytosis Aspergillus fumigatus immunotherapy mesenchymal stromal cells |
Language | English |
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Title | Impact of human mesenchymal stromal cells on antifungal host response against Aspergillus fumigatus |
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