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.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$528,293
Indirect Cost
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