Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice.
Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice.
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DOI：
10.1002/jmv.25212
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发表时间：
2018-09
影响因子：
12.7
通讯作者：
Juffermans NP
中科院分区：
文献类型：
--
作者：
van Someren Gréve F;van der Sluijs KF;Tuip AM;Schultz MJ;de Jong MD;Juffermans NP
继发性细菌性肺炎是流感的常见并发症，与高发病率和死亡率相关。我们假设用中和甲型流感抗体AT10_002治疗可以在甲型流感感染的小鼠模型中保护免受严重的继发性肺炎球菌感染。感染甲型流感（H3 N2）病毒的雄性C57 B16小鼠在感染后2天静脉注射AT10_002或对照。7天后，两组均感染肺炎链球菌，18小时后处死。与对照组相比，接受AT10_002的小鼠体重减轻较少（+1% vs − 12%，P < .001），支气管肺泡灌洗液（BALF）中的病毒载量较低（7 vs 194 RNA拷贝/μL; P < .001），并减少肺匀浆中的细菌生长（3.3 × 101 vs 2.5 × 105菌落形成单位/mg; P < .001）。与对照组相比，治疗组显示出较低的肺湿重、较低的细胞计数和较低的BALF蛋白水平。AT10_002治疗与BALF中肿瘤坏死因子-α、白细胞介素（IL）-6、细胞因子诱导的中性粒细胞趋化因子（KC）和干扰素-γ水平降低以及肺匀浆中IL-6和KC水平降低相关。在流感感染后继发性肺炎球菌肺炎的鼠模型中，抗流感抗体AT10_002治疗与体重减轻、病毒载量、细菌生长和肺损伤减少相关。
Secondary bacterial pneumonia is a frequent complication of influenza, associated with high morbidity and mortality. We hypothesized that treatment with neutralizing influenza A antibody AT10_002 protects against severe secondary pneumococcal infection in a mouse model of influenza A infection. Influenza A (H3N2) virus–infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control 2 days postinfection. Seven days later, both groups were infected with Streptococcus pneumoniae and killed 18 hours later. Mice receiving AT10_002 showed less loss of bodyweight compared with controls (+1% vs −12%, P < .001), lower viral loads in bronchoalveolar lavage fluids (BALFs) (7 vs 194 RNA copies per µL; P < .001), and reduced bacterial outgrowth in lung homogenates (3.3 × 101 vs 2.5 × 105 colony‐forming units per mg; P < .001). The treatment group showed lower pulmonary wet weights, lower cell counts, and lower protein levels in BALF compared with controls. Treatment with AT10_002 was associated with lower levels of tumor necrosis factor‐α, interleukin (IL)‐6, cytokine‐induced neutrophil chemoattractant (KC), and interferon‐γ in BALF and lower IL‐6 and KC in lung homogenates. Treatment with anti‐influenza antibody AT10_002 is associated with reduced weight loss, viral load, bacterial outgrowth, and lung injury in a murine model of secondary pneumococcal pneumonia following influenza infection.
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影响因子：
5.5
作者：
Nichol, KL
通讯作者：
Nichol, KL
DOI：
10.1164/rccm.201101-0110oc
发表时间：
2011-05-01
影响因子：
24.7
作者：
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影响因子：
168.9
作者：
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通讯作者：
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影响因子：
3.7
作者：
Grabowska, Katarzyna;Hogberg, Liselotte;Ekdahl, Karl
通讯作者：
Ekdahl, Karl