Critical role of myeloperoxidase and nicotinamide adenine dinucleotide phosphate-oxidase in high-burden systemic infection of mice with Candida albicans

Yasuaki Aratani, Fumiaki Kura, Haruo Watanabe, Hisayoshi Akagawa, Yukie Takano, Kazuo Suzuki, Mary C. Dinauer, Nobuyo Maeda, Hideki Koyama

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1833-1837
Number of pages5
JournalJournal of Infectious Diseases
Volume185
Issue number12
DOIs
StatePublished - Jun 15 2002

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