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Combined therapy of interleukin-12 and interleukin-18 against Cryptococcus neoformans infection in a murine model

Chinese Medical Journal 2003年第5期116卷 669-672页

作者：张天托 kazuyoshi kawakami Mahboob H Qureshi 唐英春 Atsushi Saito Department of Internal Medicine Third Affiliated Hospital Sun Yat-Sen University Guangzhou 510630 China Department of Internal Medicine Faculty of Medicine University of the Ryukyus Okinawa Japan

Objective To explore adverse effects of combined treatment of interleukin-12 (IL-12) and interleukin-18 (IL-18) against cryptococcosis in a murine *** Infected mice were treated with a combination of IL-12 and IL-18. Their body weight and intake of water and food were observed and recorded. Serum levels of leptin were detected with an enzyme-linked immuno sorbent assay (ELISA).Results In the combined treatment group, the intake volume of water and food were reduced, leading to weight loss and undetectable levels of leptin in the serum. These adverse effects were more profound in mice that had received higher doses of cytokines, which sometimes led to a fatal outcome. There was a significant difference compared with the control group. Neutralization of endogenous tumor necrosis factor-α (TNF-α) by its specific mAb did not alter the wasting effect of this *** The combined IL-12/IL-18 treatment may cause a number of adverse effects independent of TNF-α and leptin synthesis. Further investigations for resolving these adverse effects are required before clinical application of these cytokines.

关键词： adverse effect interleukin-12 interleukin-18 tumor necrosis factor-α cryptococcosis

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Involvement of Dectin-2 in the Innate Inflammatory Response Triggered by Influenza Virus Hemagglutinin

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Advances in Infectious Diseases 2023年第3期13卷 478-497页

作者： Hideki Yamamoto Chikako Tomiyama Sho Yamasaki Shinobu Saijo Yoichiro Iwakura kazuyoshi kawakami Department of Medical Technology Graduate School of Health Sciences Niigata University Niigata Japan Department of Molecular Immunology Research Institute for Microbial Diseases Osaka University Osaka Japan Laboratory of Molecular Immunology Immunology Frontier Research Center Osaka University Osaka Japan Project for Cytokine Research Division of Molecular Immunology Medical Mycology Research Center Chiba University Chiba Japan Center for Animal Disease Models Research Institute for Biomedical Sciences Tokyo University of Science Chiba Japan Department of Medical Microbiology Mycology and Immunology Tohoku University Miyagi Japan Department of Internal Medicine Hirose Hospital Miyagi Japan

C-type lectin receptors (CLRs) are representative pattern recognition receptors that recognize microbial polysaccharides expressed on antigen-presenting cells. In the present study, we carried out further detailed analysis on the involvement of Dectin-2, a CLR that senses high mannose polysaccharide, in innate immune responses induced by influenza virus hemagglutinin (HA). Treatment of HA with periodate or PNGase F induced lower interleukin (IL)-12p40 secretion by conventional dendritic cells (DCs) compared with the untreated group. In contrast, treatment with O-glycosidase did not affect cytokine production. Green fluorescent protein expression in canonical Dectin-2-transducing cells was approximately 3% - 12% following HA stimulation, except with the A/H1N1pdm09 subtype HA. This expression was markedly reduced in cells possessing mutated amino acids in the carbohydrate recognition domain of Dectin-2, especially following stimulation with HA derived from the A/H3N2 subtype. Interferon (IFN)-α production from CD11c+Siglec-H+PDCA-1+ plasmacytoid DCs was significantly increased in Dectin-2 knockout mice compared with wild-type mice upon stimulation with HA except for the B/Yamagata lineage HA. These results suggested that Dectin-2 is involved in initiating inflammatory responses via mannose polysaccharide on HA. However, other mechanisms may function in the antiviral response, including the type I IFN axis.

关键词： C-Type Lectin Receptors Influenza Virus Innate Immunity Type I Interferon

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Human CD4^- CD8^- Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors

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World Journal of Vaccines 2016年第2期6卷 34-41页

作者： Tomomitsu Miyasaka Yurie Watanabe Yukiko Akahori Namiko Miyamura Keiko Ishii Yuki Kinjo Yoshitsugu Miyazaki Tian-Yi Liu Yasushi Uemura kazuyoshi kawakami Department of Medical Microbiology Mycology and Immunology Tohoku University Graduate School of Medicine Sendai Japan Department of Chemotherapy and Mycoses National Institute of Infectious Diseases Tokyo Japan Division of Immunology Aichi Cancer Center Research Institute (ACCRI) Nagoya Japan Key Laboratory of Cancer Center Chinese PLA General Hospital Beijing China Division of Cancer Immunotherapy Exploratory Oncology Research & Clinical Trial Center National Cancer Center (NCC) Kashiwa Japan

Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells;for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19+CD27- (naïve) and CD19+CD27+ (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells;nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.

关键词： Invariant Natural Killer T Cells TI-2 Antigen B Cells IgM IgG

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冬虫夏草对慢性阻塞性肺疾病大鼠树突状细胞功能的影响

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中国病理生理杂志 2011年第12期27卷 2372-2375页

作者：李洪涛张天托黄静刘慧川上和羲中山大学附属第三医院呼吸内科广东广州510630 日本东北大学医学部

目的:研究冬虫夏草对慢性阻塞性肺疾病(COPD)大鼠树突状细胞(DCs)功能的影响及其分子机制。方法:将大鼠随机分为COPD模型组、冬虫夏草治疗组和正常对照组,观察各组大鼠气道病理改变,分离培养鼠DCs,ELISA法检测DCs培养上清液和DCs-T细胞... 详细信息

目的:研究冬虫夏草对慢性阻塞性肺疾病(COPD)大鼠树突状细胞(DCs)功能的影响及其分子机制。方法:将大鼠随机分为COPD模型组、冬虫夏草治疗组和正常对照组,观察各组大鼠气道病理改变,分离培养鼠DCs,ELISA法检测DCs培养上清液和DCs-T细胞共培养上清液中细胞因子含量。结果:与正常对照组相比,COPD模型组和冬虫夏草治疗组的平均肺泡计数减少(P0.05)。冬虫夏草治疗组DCs-T细胞共培养后上清液中IFN-γ水平高于COPD模型组和正常对照组(P0.05)。冬虫夏草治疗组DCs上清液中TNF-α和IL-12 p70水平高于COPD模型组和正常对照组(P<0.05)。结论:冬虫夏草可促使COPD大鼠DCs产生Th1型细胞因子,机制可能与DCs产生的IL-12 p70促进T细胞产生IFN-γ有关。

关键词：肺疾病,慢性阻塞性冬虫夏草树突状细胞

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Involvement of Dectin-2 in the Innate Inflammatory Response Triggered by Influenza Virus Hemagglutinin

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Advances in Infectious Diseases（传染病进展） 2023年第3期

作者： Hideki Yamamoto Chikako Tomiyama Sho Yamasaki Shinobu Saijo Yoichiro Iwakura kazuyoshi kawakami

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