Variable correction of host defense following gene transfer and bone marrow transplantation in murine X-linked chronic granulomatous disease

Author:

Dinauer Mary C.1,Gifford Mary A.1,Pech Nancy1,Li Ling Lin1,Emshwiller Patricia1

Affiliation:

1. From the Herman B Wells Center for Pediatric Research, Departments of Pediatrics (Hematology/Oncology) and Medical and Molecular Genetics, James Whitcomb Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN.

Abstract

Chronic granulomatous disease (CGD) is an inherited immunodeficiency in which the absence of the phagocyte superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase results in recurrent bacterial and fungal infections. A murine model of X-linked CGD (X-CGD) was used to explore variables influencing reconstitution of host defense following bone marrow transplantation and retroviral-mediated gene transfer. The outcomes of experimental infection with Aspergillus fumigatus, Staphylococcus aureus, orBurkholderia cepacia were compared in wild-type, X-CGD mice, and transplanted X-CGD mice that were chimeric for either wild-type neutrophils or neutrophils with partial correction of NADPH oxidase activity after retroviral-mediated gene transfer. Host defense to these pathogens was improved in X-CGD mice even with correction of a limited number of neutrophils. However, intact protection against bacterial pathogens required relatively greater numbers of oxidant-generating phagocytes compared to protection against A fumigatus. The host response also appeared to be influenced by the relative level of cellular NADPH oxidase activity, particularly forA fumigatus. These results may have implications for developing effective approaches for gene therapy of CGD.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference47 articles.

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3. Mutations in the X-linked and autosomal recessive forms of chronic granulomatous disease.;Roos;Blood.,1996

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