Gene Correction Reduces Cutaneous Inflammation and Granuloma Formation in Murine X-Linked Chronic Granulomatous Disease

Our laboratory previously demonstrated that X-linked chronic granulomatous disease (X-CGD) mice develop exaggerated inflammatory responses and form granulomas following intradermal challenge with sterile Aspergillus fumigatus (AF) hyphae. In this study, we examined the efficacy of retroviral-mediated gene transfer (RMGT) into X-CGD bone marrow stem cells in preventing this abnormal inflammatory response. Sterile AF or saline was injected subcutaneously into the ears of wild-type, female X-CGD carrier, X-CGD, or X-CGD mice chimeric for varying numbers of either wild-type or RMGT-corrected neutrophils. Intradermal AF induced marked inflammation at both 3 and 30 d in the X-CGD mice, but not in the carriers or the wild-type mice. Similar to wild-type mice, chimeric X-CGD mice with >20% oxidase-positive neutrophils displayed a minimal and self-limited inflammatory response. Inflammation in chimeric (both wild-type and RMGT-corrected) mice with