No abstract

Nrf2 is a redox-sensitive transcription factor that is thought to be important in protection against intracellular pathogens. To determine the protective role of Nrf2 in the host defense against Mycobacterium avium complex (MAC), both wild-type and Nrf2-deficient mice were intranasally infected with MAC bacteria. Nrf2-deficient mice were highly susceptible to MAC bacteria compared with wild-type mice. There were no significant changes in the levels of oxidative stress and Th1 cytokine production between genotypes. Comprehensive transcriptome analysis showed that the expressions of Nramp1 and HO-1 were much lower in the infected lungs, and the expression of Nramp1 was especially lower in alveolar macrophages of Nrf2-deficient mice than of wild-type mice. Electron microscopy showed that many infected alveolar macrophages from Nrf2-deficient mice contained a large number of intracellular MAC bacteria with little formation of phagolysosomes, compared with those from wild-type mice. Treatment with sulforaphane, an activator of Nrf2, increased resistance to MAC with increased lung expression of Nramp1 and HO-1 in wild-type mice. These results indicate that Nramp1 and HO-1, regulated by Nrf2, are essential in defending against MAC infection due to the promotion of phagolysosome fusion and granuloma formation, respectively. Thus, Nrf2 is thought to be a critical determinant of host resistance to MAC infection. IMPORTANCE Nontuberculous mycobacteria (NTM) are an important cause of morbidity and mortality in pulmonary infections. Among them, Mycobacterium avium complex (MAC) is the most common cause of pulmonary NTM disease worldwide. It is thought that both environmental exposure and host susceptibility are required for the establishment of pulmonary MAC disease, because pulmonary MAC diseases are most commonly observed in slender, postmenopausal women without a clearly recognized immunodeficiency. However, host factors that regulate MAC susceptibility have not been elucidated until now. This study shows that Nrf2 is a critical regulator of host susceptibility to pulmonary MAC disease by promoting phagolysosome fusion and granuloma formation via activating Nramp1 and HO-1 genes, respectively. The Nrf2 system is activated in alveolar macrophages, the most important cells during MAC infection, as both the main reservoir of infection and bacillus-killing cells. Thus, augmentation of Nrf2 might be a useful therapeutic approach for protection against pulmonary MAC disease.

Abstract. Partial or complete spontaneous cancer regression is a rare phenomenon, particularly in patients with lung cancer. This is the case report of a patient with lung cancer who exhibited spontaneous regression of the primary as well as metastatic lesions, without receiving any treatment. Spontaneous regression commenced within a week of obtaining pathological specimens by transbronchial and percutaneous biopsies from the primary lesion and metastatic lymph nodes of the left side of the neck. The reason for this phenomenon is unknown; however, we hypothesized that there may be an immunological association between the stimulus of the biopsies and the spontaneous regression. This patient should be closely followed up to monitor the clinical course of this unusual case.

Bronchial anthracofibrosis is a rare disease defined as bronchial stenosis with black pigmentation and usually not associated with artery occlusion. The patient was an 81-year-old man with silicosis. He presented with dyspnea on exertion, and pulmonary hypertension due to right upper pulmonary artery occlusion without thromboembolism was diagnosed on the basis of the results of right heart catheterization and pulmonary angiography. Bronchoscopy demonstrated bronchial anthracofibrosis in the right upper lobe. These findings suggested that the cause of PH was silicosis and pulmonary artery occlusion with bronchial anthracofibrosis. He has been treated with home oxygen therapy and tadalafil, and his symptom and 6MWD remain stable.