Myeloid progenitors protect against invasive aspergillosis andPseudomonas aeruginosa infection following hematopoietic stem cell transplantation

Abstract

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 (

Dysfunctional expansion of hematopoietic stem cells and block of myeloid differentiation in lethal sepsis

“…This concept is supported by the study of BitMansour and colleagues, in which transplantation of HSCs in combination with myeloid progenitors showed protection against P aeruginosa sepsis. 39 The effects of the isogenic P aeruginosa mutant provided us with critical insights. The nonlethal strains had in common LPS defects and resulted in infections characterized by the absence of LSK alterations and preservation of myeloid progenitors and neutrophils regeneration (N.C. and L.G.R., unpublished observations, May 2003).…”

Immune restoration following hematopoietic stem cell transplantation: an evolving target

“…5 Nonetheless, a literature addressing the immunomodulatory effects of progenitor cells is emerging. For example, murine myeloid progenitors have been shown to confer protection against bacteria and mold infection 183 as well as to attenuate alloreactive responses like GVHD. 184 Similarly, murine lymphoid progenitor cells have also been shown to confer protection against infection, specifically CMV.…”

Emerging uses for pediatric hematopoietic stem cells

“…MPs are progeny of HSCs with the potential to give rise to myeloid, erythroid, and granulocytic cells of the blood system. Infusion of these cells in neutropenic hosts has been shown to provide transient resistance to fungal and bacterial pathogens in a nonmajor histocompatibility complexdependent fashion (86,87). A recent study in an animal model indicates that MPs can be added to allogeneic HSC grafts without affecting tolerance induction (88).…”

“…Myeloid progenitor cells have been shown to be of special interest in this respect because they can be cryopreserved, used independent of major histocompatibility complex matching, and provide rapid and mostly transient engraftment that provides protection against bacterial and fungal pathogens (86,87,92).…”