IL-1 Signaling Prevents Alveolar Macrophage Depletion during Influenza and Streptococcus pneumoniae Coinfection.
IL-1 Signaling Prevents Alveolar Macrophage Depletion during Influenza and Streptococcus pneumoniae Coinfection.
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DOI：
10.4049/jimmunol.1700210
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发表时间：
2018-02-15
期刊：
影响因子：
--
通讯作者：
Sun K
中科院分区：
文献类型：
--
作者：
Bansal S;Yajjala VK;Bauer C;Sun K
流感和细菌共感染是流感流行和大流行期间人类住院和死亡的重要原因。然而，这种复杂的病毒-宿主-细菌相互作用中涉及的基本保护和致病机制仍然不完全清楚。在这项研究中，我们已经开发了轻度至致死性流感和肺炎球菌共感染模型，用于疾病发病机制的比较分析。具体而言，WT和白细胞介素-1受体1型缺陷（Il 1 r1 −/−）小鼠感染流感病毒，然后用非侵袭性肺炎球菌血清型14（Spn 14）或19 A（Spn 19 A）进行超级攻击。合并感染后进行炎症反应和动物保护的比较分析。我们发现，在没有流感感染的情况下，常驻肺泡巨噬细胞对两种肺炎球菌血清型的清除都是有效的;另一方面，它们对呼吸道控制Spn 14感染而不是Spn 19 A是必不可少的。一致的是，TNF-α和中性粒细胞在与Spn 19 A相关的继发性细菌感染中发挥代偿性保护作用;然而，在流感后肺炎球菌感染期间，AM介导的清除的基本要求显著增强了Spn 14的毒力。此外，我们表明，虽然IL-1信号传导不是宿主防御肺炎球菌感染所必需的，但它对于流感后肺炎球菌感染期间维持抗菌免疫力至关重要，正如Il 1 r1 −/−小鼠中显著加重的细菌负荷和动物死亡率所证明的那样。从机制上讲，我们表明，通过防止AM耗竭，炎症细胞因子IL-1信号传导是至关重要的参与宿主抵抗流感和肺炎球菌共感染。
Influenza and bacterial coinfection is a significant cause of hospitalization and death in humans during influenza epidemics and pandemics. However, the fundamental protective and pathogenic mechanisms involved in this complex virus-host-bacterium interaction remain incompletely understood. In this study, we have developed mild to lethal influenza and pneumococcal coinfection models for comparative analyses of disease pathogenesis. Specifically, WT and interleukin-1 receptor type 1-deficient (Il1r1−/−) mice were infected with influenza virus, and then super-challenged with noninvasive pneumococcal serotype 14 (Spn14) or 19A (Spn19A). The coinfections were followed by comparative analyses of inflammatory responses and animal protection. We found that resident alveolar macrophages are efficient in clearance of both pneumococcal serotypes in the absence of influenza infection; on the other hand, they are essential for airway control of Spn14 infection but not Spn19A. In agreement, TNF-α and neutrophils play a compensatory protective role in secondary bacterial infection associated with Spn19A; however, the essential requirement for AM-mediated clearance significantly enhances the virulence of Spn14 during post-influenza pneumococcal infection. Furthermore, we show that although IL-1 signaling is not required for host defense against pneumococcal infection alone, it is essential for sustaining antibacterial immunity during post-influenza pneumococcal infection, as evidenced by significantly aggravated bacterial burden and animal mortality in Il1r1−/− mice. Mechanistically, we show that through preventing AM depletion, inflammatory cytokine IL-1 signaling is critically involved in host resistance to influenza and pneumococcal coinfection.
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影响因子：
6.4
作者：
Karlstroem, Asa;Heston, Sarah M.;McCullers, Jonathan A.
通讯作者：
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影响因子：
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DOI：
10.1086/591708
发表时间：
2008-10-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
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通讯作者：
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影响因子：
3.1
作者：
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通讯作者：
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DOI：
10.1073/pnas.1414422112
发表时间：
2015-01-06
影响因子：
11.1
作者：
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通讯作者：
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