In contrast, treatment with the cytostatic drug cyclophosphamide prevents the recruitment of immune effector cells to the side of infection. Therefore, despite a retarded germination of conidia, fungal hyphae stay alive, which is well visualized by the massive increase in fungal DNA determined at the late stage of TSA HDAC purchase infection (Figure 2). In agreement, the bioluminescence steadily

increased under this regimen and explanted lungs show a 50 – 100 times higher light emission than observed under corticosteroid treatment. This result shows that bioluminescence measurements and DNA quantification correlate best under the cyclophophamide regimen. Although the bioluminescence readout does not correlate linearily with the fungal burden as measured by qRT-PCR, the general tendency of increasing and decreasing fungal burden as well as the impact of the inflammatory

response seems well reflected selleck kinase inhibitor by bioluminescence imaging. Impact of immunosuppression regimens on the inflammatory response In order to correlate survival curves, weight loss, fungal burden from DNA quantification and bioluminescence with histopathological findings, additional experiments were performed, in which mice were sacrificed one day (early) and three days (late) post infection. For the clodrolip condition, selleck mice were sacrificed eight days after infection to assess any later effect of treatment on mice survival. Lungs were removed, and thin sections were studied for the evaluation of the recruitment of immune effector cell lineages and fungal tissue invasion. Clodrolip treatment Lung instillation with clodrolip was expected to reduce the number of AM, which are generally denoted as the first cellular line of host innate immune defense through phagocytosis and killing of inhaled conidia. To confirm the reduction in the number

of AM, the BAL isometheptene fluid of non-infected mice were sampled two days after intranasal administration of clodrolip or liposomes, respectively. Flow cytometry was used to quantify the number of AM within the BAL fluid. The clodrolip treatment resulted in a numeric depletion of 60% of AM (8.30 × 104 ± 1 × 104 versus 2.03 × 105 ± 1.8 × 104) when compared to control liposome treated animals (p < 0.05). Furthermore, the viability of the residual AM subset was only 50% as evaluated by trypan blue staining. Taken together, clodrolip treatment depleted or resulted in the death of 80% of AM compared to control mice. When the cell populations in BAL were evaluated one day post-infection, we noted a 3.2-fold decrease (22 ± 11 versus 71 ± 28%) in the concentration of AM and a 2.6-fold increase (77.5 ± 10 versus 29 ± 28%) in the neutrophil concentration in clodrolip-treated mice compared to control liposome-treated mice (Figure 3A).