Fig. 8.
A. fumigatus PphA contributes to virulence in neutropenic mice. (A) Comparative analysis of wild-type and mutant strains in a neutropenic murine model of pulmonary aspergillosis. Mice in groups of 10 per strain were infected intranasally with a 20 μl suspension of conidiospores at a dose of 105. (B) Fungal burden results, determined by qPCR 72 h post-infection, were expressed based on 18S rRNA gene of A. fumigatus divided by the results of an intronic region of the mouse GAPDH gene. (C) Histological analysis of infection murine lung was performed 72 h after infection. Lower panels show increased magnification of the lined area from upper figure. Arrows indicate germlings. (D) TNF–α secretion from bone marrow-derived macrophages (BMDMs). The ΔpphA conidia triggered significantly increased release of TNF–α from BMDMs compared to wild–type and the reconstituted strain at 0 h time point. BMDMs from C57BL/6 mice were infected with A. fumigatus conidia, germlings, or hyphae for up to 18 h and the supernatant of cells was collected to measure the TNF-α levels by ELISA. Data show average ± standard deviation and *p ≤ 0.005 compared to the wild–type and the complemented strain.