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J Med Microbiol 55 (2006), 1291-1299; DOI: 10.1099/jmm.0.46620-0
© 2006 Society for General Microbiology
ISSN 1473-5644

Contribution of the myeloperoxidase-dependent oxidative system to host defence against Cryptococcus neoformans

Yasuaki Aratani1, Fumiaki Kura2, Haruo Watanabe2, Hisayoshi Akagawa3, Yukie Takano3, Akiko Ishida-Okawara3, Kazuo Suzuki3, Nobuyo Maeda4 and Hideki Koyama1

1 Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Totsuka, Yokohama 244-0813, Japan

2 ,3 Bacteriology2 and Bioactive Molecules3 , National Institute of Infectious Diseases, Toyama 1-23-1, Shinjuku, Tokyo 162-8640, Japan

4 Department of Pathology and Laboratory Medicine, the University of North Carolina, Chapel Hill, North Carolina 27599-7525, USA

Correspondence
Yasuaki Aratani
yaratani{at}yokohama-cu.ac.jp

Received 10 March 2006
Accepted 26 May 2006

The in vivo contribution of reactive oxygen species produced by neutrophils against Cryptococcus infection is not widely recognized. Myeloperoxidase (MPO) is a neutrophil-specific enzyme that catalyses the production of hypohalous acids such as HOCl from H2O2. This study investigated the role of MPO in immunological defence against Cryptococcus neoformans in an MPO-deficient (MPO–/–) mouse model. The survival of MPO–/– mice infected either intranasally or intravenously with C. neoformans was lower than that of identically challenged wild-type mice. The MPO–/– mice that received intranasal injection of C. neoformans had significantly larger lung fungal burdens than wild-type mice. On day 7, MPO–/– mice had a significantly higher lung concentration of interleukin (IL)-4 and lower concentrations of IL-2, IL-12p70 and interferon (IFN)-{gamma} than wild-type mice, suggesting a weak Th1 response in the MPO–/– mice to C. neoformans. Pathologically, the MPO–/– mice with intranasal infection showed more severe pneumonia than wild-type mice, which was associated with an increase in the levels of IL-1{alpha}/ß in the lungs. In addition, in MPO–/– mice, the pulmonary infection disseminated to the brain with occasional meningitis. The keratinocyte-derived cytokine (KC) level in the brain of infected MPO–/– mice was higher than that of control mice. Both intranasal and intravenous infections resulted in a higher number of fungi in the spleen of MPO–/– mice compared to wild-type, suggesting decreased resistance to C. neoformans not only in the lungs but also in the spleen in the absence of MPO. Taken together, these data suggest a major role of MPO in the response to cryptococcal infection.

Abbreviations: H&E, haematoxylin and eosin; IFN, interferon; IL, interleukin; KC, keratinocyte-derived cytokine; MPO, myeloperoxidase.




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