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M-CSF improves protection against bacterial and fungal infections after hematopoietic stem/progenitor cell transplantation

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Official URL:https://doi.org/10.1084/jem.20151975
PubMed:View item in PubMed
Creators Name:Kandalla, P.K. and Sarrazin, S. and Molawi, K. and Berruyer, C. and Redelberger, D. and Favel, A. and Bordi, C. and de Bentzmann, S. and Sieweke, M.H.
Journal Title:Journal of Experimental Medicine
Journal Abbreviation:J Exp Med
Volume:213
Number:11
Page Range:2269-2279
Date:10 October 2016
Keywords:Aspergillus, Blood Glucose, Blood Platelets, Cell Differentiation, Cell Lineage, Cell Self Renewal, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Inbred C57BL Mice, Macrophage Colony-Stimulating Factor, Myelopoiesis, Pseudomonas Infections, Pseudomonas aeruginosa, Animals, Mice
Abstract:Myeloablative treatment preceding hematopoietic stem cell (HSC) and progenitor cell (HS/PC) transplantation results in severe myeloid cytopenia and susceptibility to infections in the lag period before hematopoietic recovery. We have previously shown that macrophage colony-stimulating factor (CSF-1; M-CSF) directly instructed myeloid commitment in HSCs. In this study, we tested whether this effect had therapeutic benefit in improving protection against pathogens after HS/PC transplantation. M-CSF treatment resulted in an increased production of mature myeloid donor cells and an increased survival of recipient mice infected with lethal doses of clinically relevant opportunistic pathogens, namely the bacteria Pseudomonas aeruginosa and the fungus Aspergillus fumigatus. M-CSF treatment during engraftment or after infection efficiently protected from these pathogens as early as 3 days after transplantation and was effective as a single dose. It was more efficient than granulocyte CSF (G-CSF), a common treatment of severe neutropenia, which showed no protective effect under the tested conditions. M-CSF treatment showed no adverse effect on long-term lineage contribution or stem cell activity and, unlike G-CSF, did not impede recovery of HS/PCs, thrombocyte numbers, or glucose metabolism. These results encourage potential clinical applications of M-CSF to prevent severe infections after HS/PC transplantation.
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Item Type:Article

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