Nitric Oxide Contributes to the Pathogenesis of Nocardia farcinica Infection in BALB/c Mice and Alveolar MH-S Macrophages

<i>Nocardia</i>, a rare but life-threatening pathogen, can invade multiple tissues and organs, such as lungs, brain, skin and soft tissue. In this study, we determined whether nitric oxide (NO) contributes to the severity of experimental pulmonary nocardiosis. BALB/c mice with or without aminoguanidine (AG) treatment were infected with <i>N. farcinica</i> through intranasal or intraperitoneal routes. Over experimental period, weight and mortality were monitored, and lung tissues were collected for NO production, cytokines detection, histopathological analysis, and bacterial load assessment. Next, alveolar MH-S macrophages were treated with various inhibitors to explore the impacts of NO, MAPK, and NF-κB against <i>N. farcinica</i> infection. AG treatment improved weight loss, lowered pulmonary bacterial load, and attenuated inflammatory response in infected mice. Similar effects were observed in alveolar MH-S macrophages. And all AG-treated mice survived infection. Furthermore, we suggest that NO is induced by <i>N. farcinica</i> through MAPK JNK and NF-κB signaling. Our study demonstrates the causative role of inducible NO on the severity of <i>N. farcinica</i> infection.