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

Prashanth Kandalla (1) , Sandrine Sarrazin (1) , Kaaweh Molawi (1, 2) , Carole Berruyer (1) , David Redelberger (3, 4) , Anne Favel (5) , Christophe Bordi (3, 4) , Sophie de Bentzmann (3, 4) , Michael H. Sieweke (1)

1 CIML - Centre d'Immunologie de Marseille - Luminy
2 MDC - Max Delbrück Centrum für Molekulare Medizin
3 IMM - Institut de Microbiologie de la Méditerranée
4 LISM - Laboratoire d'ingénierie des systèmes macromoléculaires
5 BBF - Biodiversité et Biotechnologie Fongiques

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.

Keywords: cellule souche; infection fongique; cellule hematopoietique; infection bactérienne; transplantation cellulaire; pseudomonas aeruginosa; aspergillus fumigatus; lignation cellulaire

Domains: Life Sciences [q-bio]; Immunology

Prashanth Kandalla, Sandrine Sarrazin, Kaaweh Molawi, Carole Berruyer, David Redelberger, et al.. M-CSF improves protection against bacterial and fungal infections after hematopoietic stem/progenitor cell transplantation. Journal of Experimental Medicine, 2016, 213 (11), pp.2269-2279. ⟨10.1084/jem.20151975⟩. ⟨hal-01770253⟩