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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-05-1552.
Submitted May 28, 2002
Accepted July 22, 2002
Myeloid progenitors protect against invasive aspergillosis and Pseudomonas aeruginosa infection following hematopoietic stem cell transplantation
Andrew BitMansour, Stacy M Burns, David Traver, Koichi Akashi, Christopher H Contag, Irving L Weissman, and Janice M Y Brown*
Medicine/BMT, Stanford University, Stanford, CA, USA
Medicine/Microbiology/Immunology, Stanford University, Stanford, CA, USA
Medicine/Pathology, Stanford University, Stanford, CA, USA
* Corresponding author; email: wesbrown{at}stanford.edu.
Myelotoxic treatments for oncologic diseases are often complicated by neutropenia, which renders patients susceptible to potentially lethal infections. In these studies of murine hematopoietic stem cell transplantation (HSCT), co-transplantation of lineage-restricted progenitors known as common myeloid progenitors (CMP) and granulocyte-monocyte progenitors (GMP) protects against death following otherwise lethal challenge with either of two pathogens associated with neutropenia: Aspergillus fumigatus and Pseudomonas aeruginosa. Co-transplantation of CMP/GMP resulted in a significant and rapid increase in the absolute number of myeloid cells in the spleen, the majority of which were derived from the donor CMP/GMP. Despite persistent peripheral neutropenia, improved survival correlated with the measurable appearance of progenitor-derived myeloid cells in the spleen. A marked reduction or elimination of tissue pathogen load was confirmed by culture and correlated with survival. Localization of infection by P. aeruginosa and extent of disease was also assessed by in vivo bioluminescent imaging using a strain of P. aeruginosa engineered to constitutively express a bacterial luciferase. Imaging confirmed that transplantation with a graft containing hematopoietic stem cells and CMP/GMP reduced the bacterial load as early as eighteen hours after infection. These results demonstrate that enhanced reconstitution of a tissue myeloid pool offers protection against lethal challenge with serious fungal and bacterial pathogens.
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