Detailed characterisation of invasive aspergillosis in a murine model of X-linked chronic granulomatous disease shows new insights in infections caused byversus.

Abstract

INTRODUCTION: Invasive aspergillosis (IA) is the most prevalent infectious complication in patients with chronic granulomatous disease (CGD). Yet, understanding of fungal pathogenesis in the CGD host remains limited, particularly with regards toinfection. METHODS: We have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies betweenand, comparing infection in both X-linked CGD (gp91) mice and their parent C57BL/6 (WT) mice. A 14-colour flow cytometry panel was used to assess the cell dynamics over the course of infection, with parallel assessment of pulmonary cytokine production and lung histology. RESULTS: We observed a lack of association between pulmonary pathology and infection outcome in gp91mice, with no significant mortality ininfected mice. An overwhelming and persistent neutrophil recruitment and IL-1 release in gp91mice following bothandinfection was observed, with divergent macrophage, dendritic cell and eosinophil responses and distinct cytokine profiles between the two infections. CONCLUSION: We have provided an in-depth characterisation of the immune response to pulmonary aspergillosis in an X-linked CGD murine model. This provides the first description of distinct pulmonary inflammatory environments inandinfection in X-linked CGD and identifies several new avenues for further research.