Figure 7
From: The contribution of PARs to inflammation and immunity to fungi
Divergent role of PAR2 in A. fumigatus or C. albicans infection. WT C57BL6 (n=12), PAR2-deficient (par2−/−) (n=8) or overexpressing (par2-Tg) (n=8) mice were infected as described in the legend of Figure 2. (a) Histologic analysis of lungs (4 days after the Aspergillus infection) showing signs of exaggerated inflammatory reaction (black arrows, inset), fungal growth (white arrows, inset), and parenchymal destruction in par2−/− mice and attenuation in par2-Tg mice. Histological analysis of the stomach (6 days after the Candida infection) showed reduced inflammatory reaction in par2-Tg mice and no exacerbation in par2−/− mice. The tissue inflammatory pathology in response to either fungus was not different between WT C57BL6 and BALB/c mice (the corresponding WT of par2-Tg mice), and organs from uninfected par2−/− or par2-Tg mice showed no obvious signs of tissue alteration compared to WT mice (data not shown). Bars indicate magnification. One representative of three experiments is shown. (b) Oxidant (O2−) and MMP9 production were assessed in the lungs or stomach homogenates of infected mice (AU, index of scanning densitometry). Shown in the inset is the O2− production in vitro of par2−/− PMNs in response to conidia upon exposure to PAR1 antagonist. (c) Opposite pattern of TNF-α/IL-10 production in lung homogenates from par2−/− or par2-Tg mice. Levels of cytokines (pg ml−1, by enzyme-linked immunosorbant assay) in lung homogenates from uninfected mice were comparable among groups. *P<0.05, par2−/− or par2-Tg vs. WT mice and treated vs. untreated PMNs. IL-10, interleukin 10; MMP9, matrix metalloproteinase 9; PAR, protease-activated receptor; PMN, polymorphonuclear neutrophil; TNF-α, tumor necrosis factor-α; WT, wild type.
