M-CSF improves protection against bacterial and fungal infections after hematopoietic stem/progenitor cell transplantation.
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.
Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, 13288 Marseille, France.
Prashanth K
0000-0002-5405-7286
PK
Kandalla
Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, 13288 Marseille, France.
Sandrine
S
Sarrazin
Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, 13288 Marseille, France.|Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, 13125 Berlin, Germany.
Kaaweh
0000-0003-2717-3764
K
Molawi
Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, 13288 Marseille, France.
Carole
0000-0003-0244-8071
C
Berruyer
Centre National de la Recherche Scientifique, Laboratoire d' Ingenierie des Systemes Macromoleculaires, Institut de Microbiologie de la Mediterranee, Aix Marseille Université, 13402 Marseille, France.
David
D
Redelberger
Institute National de la Recherche Agronomique, Unite Mixte de Recherche 1163 BBF, Aix Marseille Université, 13288 Marseille, France.
Anne
0000-0003-2255-3637
A
Favel
Centre National de la Recherche Scientifique, Laboratoire d' Ingenierie des Systemes Macromoleculaires, Institut de Microbiologie de la Mediterranee, Aix Marseille Université, 13402 Marseille, France.
Christophe
0000-0002-2877-6068
C
Bordi
Centre National de la Recherche Scientifique, Laboratoire d' Ingenierie des Systemes Macromoleculaires, Institut de Microbiologie de la Mediterranee, Aix Marseille Université, 13402 Marseille, France.
Sophie
0000-0002-9038-0662
S
de Bentzmann
Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, 13288 Marseille, France sieweke@ciml.univ-mrs.fr.|Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtzgemeinschaft, 13125 Berlin, Germany.
Michael H
MH
Sieweke
D000818:Animals; D001228:Aspergillosis / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control*; D001230:Aspergillus / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000187:drug effects; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D016173:Macrophage Colony-Stimulating Factor