Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans.
Oxygen metabolites generated by myeloperoxidase (MPO) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase contribute to microbial killing by phagocytes. To compare the importance of the 2 enzymes for host defense, MPO-deficient (MPO(-/-)) mice and NADPH-oxidase-deficient mice with chronic granulomatous disease (CGD mice) were intraperitoneally infected with 3 different doses of Candida albicans, and their infection severity was analyzed. CGD mice had increased mortality and exhibited increased tissue fungal burden in a dose-dependent manner, whereas normal mice showed no symptoms. Of interest, at the highest dose, the mortality of MPO(-/-) mice was comparable to that of CGD mice, but at the lowest dose, it was the same as that of normal mice. At the middle dose, the number of fungi disseminated into various organs of the MPO(-/-) mice was comparable to that of the CGD mice at day 6 of infection, but it was significantly lower at day 14. These results suggest that MPO and NADPH-oxidase are equally important for early host defense against a large inoculum of Candida.
Aratani
Yasuaki
Y
Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Totsuka, Yokohama 244-0813, Japan. yaratani@yokohama-cu.ac.jp
Kura
Fumiaki
F
Watanabe
Haruo
H
Akagawa
Hisayoshi
H
Takano
Yukie
Y
Suzuki
Kazuo
K
Dinauer
Mary C
MC
Maeda
Nobuyo
N
Koyama
Hideki
H
D000818:Animals; D002177:Candidiasis / Q000503:physiopathology*; D004198:Disease Susceptibility; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000502:physiology*; D009195:Peroxidase / Q000502:physiology*; D010586:Phagocytes / Q000276:immunology
D009195:Peroxidase; D019255:NADPH Oxidases