Cryptococcus neoformans inhibits nitric oxide synthesis caused by CpG-oligodeoxynucleotide-stimulated macrophages in a fashion independent of capsular polysaccharides
Article first published online: 8 APR 2008
©2008 The Societies and Blackwell Publishing Asia Pty Ltd
Microbiology and Immunology
Volume 52, Issue 3, pages 171–179, March 2008
How to Cite
Xiao, G., Miyazato, A., Inden, K., Nakamura, K., Shiratori, K., Nakagawa, K., Miyazawa, T., Suzuki, K., Kaku, M. and Kawakami, K. (2008), Cryptococcus neoformans inhibits nitric oxide synthesis caused by CpG-oligodeoxynucleotide-stimulated macrophages in a fashion independent of capsular polysaccharides. Microbiology and Immunology, 52: 171–179. doi: 10.1111/j.1348-0421.2008.00019.x
- Issue published online: 8 APR 2008
- Article first published online: 8 APR 2008
- Received 10 August 2007; accepted 9 December 2007.
- Cryptococcus neoformans;
- nitric oxide
Cryptococcus neoformans is eradicated by macrophages via production of NO. Unmethylated CpG-ODN protect mice from infection with this fungal pathogen by inducing IFN-γ. The present study was designed to elucidate the effect of C. neoformans on the synthesis of NO by alveolar macrophages. For this purpose, MH-S, an alveolar macrophage cell line, was stimulated with CpG-ODN in the presence of IFN-γ. A highly virulent strain of C. neoformans with thick capsule suppressed the production of NO. Capsular polysaccharides were not essential for this suppression, because there was no difference between acapsular mutant (Cap67) and its parent strain. Physical or close interaction of Cap67 with MH-S was necessary, as shown by the loss of such effect when direct contact was interfered by nitrocellulose membrane. Similar effects were observed by disrupted as well as intact Cap67. Whereas the inhibitory effect of intact Cap67 was completely abrogated by heat treatment, disrupted Cap67 did not receive such influence. Finally, disrupted Cap67 did not show any inhibitory effect on the TLR9-mediated activation of NF-κB in a luciferase reporter assay with HEK293T cells, although the TLR4-mediated activation was suppressed. These results revealed that C. neoformans suppressed the synthesis of NO by CpG-ODN and IFN-γ-stimulated macrophages in a fashion independent of capsular polysaccharides, although the precise mechanism remains to be elucidated.