Protection against lethal Aspergillus fumigatus infection in mice by allogeneic myeloid progenitors is not major histocompatibility complex restricted.
Invasive fungal infections are a leading cause of morbidity and mortality after myelotoxic chemotherapy or radiation exposure. The resulting depletion of myeloid precursors under these conditions appears to be the factor that limits approaches to accelerate immune reconstitution. In a murine model of myeloablation after radiation exposure, we demonstrated that highly purified common myeloid and granulocyte-monocyte progenitors (CMPs/GMPs) accelerated myeloid recovery and, thus, enhanced innate immunity as measured by survival after a lethal challenge with Aspergillus fumigatus. Of greatest significance was the demonstration that the protection afforded by CMPs/GMPs was not major histocompatibility complex restricted. Furthermore, the effect of CMP/GMP cellular therapy was additive with that of liposomal amphotericin B treatment. These observations greatly expand the potential donor pool and, thus, the clinical utility of CMP/GMP cellular therapy in patients with myeloid depletion.
Arber
Caroline
C
Department of Medicine, Division of Bone Marrow Transplantation, Stanford University School of Medicine, Stanford, California 94305, USA.
Bitmansour
Andrew
A
Shashidhar
Sumana
S
Wang
Sophia
S
Tseng
Benjamin
B
Brown
Janice M Y
JM
D000818:Animals; D001228:Aspergillosis / Q000209:etiology / Q000517:prevention & control*; D001232:Aspergillus fumigatus; D001853:Bone Marrow / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023461:Myeloid Progenitor Cells / Q000276:immunology*; D011833:Radiation Injuries, Experimental / Q000150:complications / Q000628:therapy; D014184:Transplantation, Homologous