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Impaired host defence against Mycobacterium avium in mice with chronic granulomatous disease
Authors:M Fujita  E Harada  T Matsumoto  Y Mizuta  S Ikegame  H Ouchi  I Inoshima  S Yoshida  K Watanabe  Y Nakanishi
Institution:*Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan;Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan;Department of Respiratory Medicine, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
Abstract:Patients with chronic granulomatous disease (CGD), an inherited disorder of phagocytic cells, often contract recurrent life‐threatening bacterial and fungal infections. CGD is considered to arise from a functional defect of the O2‐generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. To determine whether or not NADPH oxidase is crucial to the host defence against Mycobacterium avium, we investigated the response against M. avium using CGD model mice (gp91‐phox) of C57BL/6 strain. A tracheal injection of 1 × 107 colony‐forming units (CFU)/head of M. avium strain FN into the CGD mice resulted in a pulmonary infection, while also increasing the mortality rate. In contrast, normal C57BL/6 mice injected with same dose of the organisms did not develop severe pulmonary infection and were able to survive through 2 months of observation. The macrophages obtained from the CGD mice were observed to have a higher burden of the bacterial growth than macrophages from normal C57BL/6 mice. These results suggest that the defect of the NADPH oxidase function impairs the host defence against M. avium infection.
Keywords:animal study  innate immunity  mycobacteriosis  NADPH oxidase  opportunistic infection
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