Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.
Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.
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DOI：
10.1371/journal.ppat.1005875
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发表时间：
2016-09
期刊：
影响因子：
6.7
通讯作者：
Russell CJ
中科院分区：
文献类型：
--
作者：
Mostafa HH;Vogel P;Srinivasan A;Russell CJ
在免疫功能低下的患者中，副流感病毒（PIV）感染传播至下呼吸道（LRT）的可能性增加，导致发病率和死亡率增加。了解促进病毒传播到LRT的免疫缺陷将有助于制定更好的管理方案。在这项研究中，我们用地塞米松和/或环磷酰胺免疫抑制小鼠，然后通过使用非侵入性生物发光成像系统和报告仙台病毒（鼠PIV 1型）监测病毒感染扩散到LRT。我们的研究结果表明，免疫抑制导致延迟病毒清除和增加病毒载量在肺部。停止环磷酰胺治疗后，病毒清除发生在仙台特异性抗体反应产生之前，并与中性粒细胞，T淋巴细胞和自然杀伤（NK）细胞的反弹相吻合。使用抗Ly 6 G抗体的中性粒细胞抑制对感染清除没有影响，使用抗NK抗体的NK细胞抑制延迟清除，使用抗CD 3抗体的T细胞抑制导致没有清除（慢性感染）。造血生长因子G-CSF和GM-CSF的治疗性使用对感染的清除没有影响。相反，用仙台病毒特异性多血清或单克隆抗体治疗限制了病毒扩散到肺部并加速了清除。总体而言，非侵入性生物发光被证明是一个有用的工具，研究呼吸道病毒的进展，揭示作用的NK细胞和T细胞，但不是中性粒细胞，在仙台病毒清除后，用地塞米松和环磷酰胺治疗。病毒特异性抗体似乎具有治疗潜力。副流感病毒（PIV）是主要的呼吸道病原体，几乎感染所有5岁以下的儿童。在免疫功能低下的患者中，感染特别严重并危及生命。尽管免疫功能低下患者中的感染很常见，但目前没有有效的治疗或预防措施。在这里，我们研究了非侵入性生物发光成像的PIV感染的进展，免疫功能低下的小鼠。我们还测试了用各种干预方法治疗感染的免疫功能低下小鼠的结果，这些干预方法旨在通过特异性抗体靶向病毒或使用广泛增加中性粒细胞或B-和T-细胞的药物调节宿主的免疫系统。与需要在规定时间点对动物组实施安乐死的经典技术相比，生物发光成像被证明能够以更高的精度、更小的变异性和更少的动物来量化呼吸道感染。免疫功能低下宿主感染的非侵入性成像也被证明非常适合于跟踪持续感染和开发新的预防和治疗策略。
In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. Parainfluenza viruses (PIV) are major respiratory pathogens that infect almost all children before the age of 5. Infection is particularly severe and life threatening in immunocompromised patients. Although infections among immunocompromised patients are common, there are currently no effective therapeutic or preventive measures. Here, we studied the progression of PIV infection in living, immunocompromised mice by non-invasive bioluminescence imaging. We also tested the outcome of treating infected, immunocompromised mice with various intervention approaches designed to target the virus by specific antibodies or modulating the host’s immune system using drugs that increase neutrophils or B- and T-cells broadly. Bioluminescence imaging was demonstrated to quantify respiratory infection with greater precision, less variability, and fewer animals than classic techniques that require euthanizing groups of animals at defined time points. Non-invasive imaging of infection in immunocompromised hosts is also shown to be well suited to track sustained infections and develop novel preventive and therapeutic strategies.
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影响因子：
6.4
作者：
Buisman, AM;Langermans, JAM;vanFurth, R
通讯作者：
vanFurth, R
影响因子：
20.3
作者：
Cifone, MG;Migliorati, G;Riccardi, C
通讯作者：
Riccardi, C
DOI：
10.1111/tid.12177
发表时间：
2014-02
期刊：
Transplant infectious disease : an official journal of the Transplantation Society
影响因子：
--
作者：
Chalkias S;Mackenzie MR;Gay C;Dooley C;Marty FM;Moss RB;Li T;Routh RL;Walsh SR;Tan CS
通讯作者：
Tan CS
影响因子：
6.7
作者：
Burke CW;Mason JN;Surman SL;Jones BG;Dalloneau E;Hurwitz JL;Russell CJ
通讯作者：
Russell CJ
DOI：
10.1056/nejmoa1204630
发表时间：
2013-02-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Edwards KM;Zhu Y;Griffin MR;Weinberg GA;Hall CB;Szilagyi PG;Staat MA;Iwane M;Prill MM;Williams JV;New Vaccine Surveillance Network
通讯作者：
New Vaccine Surveillance Network