Despite the low correlation of fungal biomass and bioluminescence at late time points after infection in the cortisone acetate and RB6-8C5 treatments, a good correlation between the increase in the fungal biomass and the bioluminescence was observed under the cyclophosphamide regimen. Under this treatment, although the growing hyphae were responsible for diffuse parenchyma lesions, the accessibility of oxygen remains possible in the absence of inflammation. At late time points, an ongoing increase of the

luminescence signal reflects the increase of biomass. Therefore, cyclophosphamide Rabusertib datasheet immunosuppression seems best suited to follow the effect of antifungal drug

treatment on clearance of fungal infections. This study additionally allowed gaining new insight concerning the impact of different immune effector cells in the defense against invasive aspergillosis. Alveolar macrophages (AM) were assumed to play an important role in clearance of conidia from tissues and provide a “”first-line of defense”" against A. fumigatus infections [3]. AM are thought to trigger the recruitment of immune effector cells BAY 11-7082 molecular weight to the site of infection after recognition and phagocytosis of conidia [27] through the release of inflammatory and chemotactic mediators. Due to the importance of AM in conidial host defense, we expected that their reduction by the clodrolip

treatment would increase the susceptibility of mice to IA. This assumption was not confirmed experimentally. Intranasally clodrolip-treated mice showed a 80% reduction in the number and viability of AM [28, 29], but a 2.6 fold increase in the number of BAL fluid neutrophils, one day post-infection. A significant increase in the neutrophil number in BAL fluid of macrophage-depleted (clodrolip-treated) mice 24 hours PTK6 after instillation of Pseudomonas aeruginosa has already been reported. learn more However, in this work macrophage-deficient mice showed impaired bacterial clearance [30]. In contrast, in our model, neutrophil migration into the airways of macrophage-depleted infected mice is likely to have prevented conidial germination per se. Supporting this idea, we found that the thoracic region or BAL fluid of AM-depleted animals only showed a slight increase in bioluminescence above control levels (Figure 3). This finding correlated with survival data and histopathological findings, demonstrating an absence of conidial germination in AM-depleted mice.