RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis
文献类型：期刊论文
| 作者 | Fa, Zhenzong1,2,3; Pan, Weihua1,2; Liao, Wanqing1,2; Fang, Wei2; Olszewski, Michal A.2,3; Xu, Jintao3; Xie, Qun4,5; Deng, Xiaoming4; Zhang, Haibing5; Zhang, Haiwei5 |
| 刊名 | FRONTIERS IN IMMUNOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 8期号:-页码:1055 |
| 关键词 | Cryptococcus neoformans immune responses inflammation Fas-associated death domain receptor-interacting serine/threonine kinase 3 |
| ISSN号 | 1664-3224 |
| DOI | 10.3389/fimmu.2017.01055 |
| 文献子类 | Article |
| 英文摘要 | Fas-associated death domain (FADD) and receptor interacting protein kinase 3 (RIPK3) are multifunctional regulators of cell death and immune response. Using a mouse model of cryptococcal infection, the roles of FADD and RIPK3 in anti-cryptococcal defense were investigated. Deletion of RIPK3 alone led to increased inflammatory cytokine production in the Cryptococcus neoformans-infected lungs, but in combination with FADD deletion, it led to a robust Th1-biased response with M1-biased macrophage activation. Rather than being protective, these responses led to paradoxical C. neoformans expansion and rapid clinical deterioration in Ripk3(-/-) and Ripk3(-/-) Fadd(-/-) mice. The increased mortality of Ripk3-/-and even more accelerated mortality in Ripk3(-/-) Fadd(-/-) mice was attributed to profound pulmonary damage due to neutrophil-dominant infiltration with prominent upregulation of pro-inflammatory cytokines. This phenomenon was partially associated with selective alterations in the apoptotic frequency of some leukocyte subsets, such as eosinophils and neutrophils, in infected Ripk3(-/-) Fadd(-/-) mice. In conclusion, our study shows that RIPK3 in concert with FADD serve as physiological "brakes,"preventing the development of excessive inflammation and Th1 bias, which in turn contributes to pulmonary damage and defective fungal clearance. This novel link between the protective effect of FADD and RIPK3 in antifungal defense and sustenance of immune homeostasis may be important for the development of novel immunomodulatory therapies against invasive fungal infections. |
| 学科主题 | Immunology |
| WOS关键词 | NECROSIS-FACTOR-ALPHA ; IMMUNE-RESPONSE ; NEOFORMANS INFECTION ; DENDRITIC CELLS ; INFLAMMATION ; APOPTOSIS ; HOST ; FADD ; MACROPHAGES ; FADD/MORT1 |
| 语种 | 英语 |
| WOS记录号 | WOS:000409055200001 |
| 出版者 | FRONTIERS MEDIA SA |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1090]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Changzheng Hosp, Dept Dermatol & Venereol, PLA Key Lab Mycosis, Shanghai, Peoples R China; 2.Second Mil Med Univ, Shanghai Inst Med Mycol, Shanghai Key Lab Mol Med Mycol, Shanghai, Peoples R China; 3.Univ Michigan Hlth Syst, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA; 4.Second Mil Med Univ, Changhai Hosp, Dept Anesthesiol & Intens Care, Shanghai, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab Nutr & Metab, Shanghai, Peoples R China; 6.Fudan Univ, Huashan Hosp, Dept Dermatol, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Fa, Zhenzong,Pan, Weihua,Liao, Wanqing,et al. RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis[J]. FRONTIERS IN IMMUNOLOGY,2017,8(-):1055. |
| APA | Fa, Zhenzong.,Pan, Weihua.,Liao, Wanqing.,Fang, Wei.,Olszewski, Michal A..,...&,.(2017).RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis.FRONTIERS IN IMMUNOLOGY,8(-),1055. |
| MLA | Fa, Zhenzong,et al."RIPK3/Fas-Associated Death Domain Axis Regulates Pulmonary Immunopathology to Cryptococcal Infection Independent of Necroptosis".FRONTIERS IN IMMUNOLOGY 8.-(2017):1055. |
入库方式： OAI收割
来源：上海营养与健康研究所
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