A current focus of this project is to characterize the aberrant function of antigen presenting cell (dendritic cells, macrophages) from p47phox-/- mice to understand the consequences in host defense against autoimmune disease. In addition to our investigations to systematically characterize p47phox-/- immune cell function, we worked collaboratively with the NIAID comparative medicine branch to show that p47phox-/- mice spontaneously develop severe diffuse progressive macrophage pneumonia that is 100% fatal in mice that remain free of infection. The predominant lung lesion is the development of macrophage hyperplasia with intracellular eosinophilic crystals and a Chitinase-like protein (Ym1/Ym2). In addition spleen, LN and bone marrow macrophages also develop proliferative macrophage foci. We have also found that aging p47phox-/- mice develop a membranoproliferative glomerulonephritis, with T cell infiltrates, independent of the macrophage pneumonia.
|Liu, Qi; Cheng, Lily I; Yi, Liang et al. (2009) p47phox deficiency induces macrophage dysfunction resulting in progressive crystalline macrophage pneumonia. Am J Pathol 174:153-63|