NADPH Oxidase but not Myeloperoxidase Protects Lymphopenic Mice from Spontaneous Multi-Organ Infections (44.9)

Abstract

Abstract The objective of this study was to define the role that NADPH oxidase or myeloperoxidase (MPO) plays in host defense in lymphopenic mice. To do this we crossed gp91 phox deficient (gp91 ko) or MPO ko mice with mice deficient in recombinase activating gene-1 (RAG ko) to generate lymphopenic offspring deficient in either NADPH oxidase or MPO. We found that neither gp91 ko, MPO ko mice nor RAG ko mice developed spontaneous infections when raised under specific pathogen free (SPF) conditions and all animals lived normal life spans. In contrast, gp91/RAG double deficient (gp91/RAG DKO) but not MPO/RAG DKO mice developed spontaneous multi-organ bacterial and fungal infections early in life and lived only a few months. Addition of antibiotics to the drinking water attenuated some of the infections and increased modestly the survival of these mice. The enhanced mortality of the gp91/RAG DKO mice was not due to defects in inflammatory cell recruitment or NO synthase (iNOS) activity as the number of elicited PMNs and macrophages as well as PMN and macrophage-derived production of nitric oxide in these mice were similar to wt, gp91 ko or RAG ko mice. Taken together, our data suggest that that NADPH oxidase but not MPO (or iNOS) is required for host defense in lymphopenic mice and that lymphocytes and NADPH oxidase may compensate for each others deficiency in providing resistance to spontaneous infections (Supported by DK64023).