Cryptococcus neoformans inhibits nitric oxide synthesis caused by CpG-oligodeoxynucleotide-stimulated macrophages in a fashion independent of capsular polysaccharides
Corresponding Author
Gang Xiao
Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University
Correspondence Kazuyoshi Kawakami, Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University, 2-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan. Tel: +81 22 717 7946; fax: +81 22 717 7910; email: [email protected]
*Present address: Department of Laboratory Medicine, 6th Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Search for more papers by this authorAkiko Miyazato
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
Search for more papers by this authorKen Inden
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
Search for more papers by this authorKiwamu Nakamura
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
Search for more papers by this authorKohei Shiratori
Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University
Search for more papers by this authorKiyotaka Nakagawa
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University
Search for more papers by this authorTeruo Miyazawa
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University
Search for more papers by this authorKazuo Suzuki
Department of Immunology, Inflammatory Program, Chiba University School of Medicine, Chiba, Japan
Search for more papers by this authorMitsuo Kaku
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
CRESCENDO (Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation) Project, Tohoku University
Infection-Control Research Center, Tohoku University Hospital, Sendai
Search for more papers by this authorKazuyoshi Kawakami
Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University
Infection-Control Research Center, Tohoku University Hospital, Sendai
Search for more papers by this authorCorresponding Author
Gang Xiao
Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University
Correspondence Kazuyoshi Kawakami, Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University, 2-1 Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan. Tel: +81 22 717 7946; fax: +81 22 717 7910; email: [email protected]
*Present address: Department of Laboratory Medicine, 6th Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Search for more papers by this authorAkiko Miyazato
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
Search for more papers by this authorKen Inden
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
Search for more papers by this authorKiwamu Nakamura
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
Search for more papers by this authorKohei Shiratori
Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University
Search for more papers by this authorKiyotaka Nakagawa
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University
Search for more papers by this authorTeruo Miyazawa
Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University
Search for more papers by this authorKazuo Suzuki
Department of Immunology, Inflammatory Program, Chiba University School of Medicine, Chiba, Japan
Search for more papers by this authorMitsuo Kaku
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine
CRESCENDO (Comprehensive Research and Education Center for Planning of Drug Development and Clinical Evaluation) Project, Tohoku University
Infection-Control Research Center, Tohoku University Hospital, Sendai
Search for more papers by this authorKazuyoshi Kawakami
Microbiology and Immunology, Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Tohoku University
Infection-Control Research Center, Tohoku University Hospital, Sendai
Search for more papers by this authorABSTRACT
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.
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