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 in A. fumigatus and A. nidulans infection in X-linked CGD and identifies several new avenues for further research.
Methods
We have used a murine model of X-linked CGD to investigate how the pathogenesis of IA varies between A. fumigatus and A. nidulans, 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 gp91-/- mice, with no significant mortality in A. nidulans infected mice. An overwhelming and persistent neutrophil recruitment and IL-1 release in gp91-/- mice following both A. fumigatus and A. nidulans infection was observed, with divergent macrophage, dendritic cell and eosinophil responses and distinct cytokine profiles between the two infections.