TLR7 Contributes to the Rapid Progression but Not to the Overall Fatal Outcome of Secondary Pneumococcal Disease following Influenza A Virus Infection
TLR7 Contributes to the Rapid Progression but Not to the Overall Fatal Outcome of Secondary Pneumococcal Disease following Influenza A Virus Infection
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TLR7 导致甲型流感病毒感染后继发性肺炎球菌疾病的快速进展，但不导致总体致命结果
DOI：
10.1159/000345112
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发表时间：
2013
影响因子：
5.3
通讯作者：
Gunzer M
中科院分区：
文献类型：
--
作者：
Stegemann-Koniszewski S;Gereke M;Orrskog S;Lienenklaus S;Pasche B;Bader SR;Gruber AD;Akira S;Weiss S;Henriques-Normark B;Bruder D ;Gunzer M
细菌重复感染风险的增加大大增加了甲型流感病毒（IAV）流行造成的死亡率。虽然这种致命协同作用的机制基础尚不清楚，但已证明通过病毒感染的免疫调节参与其中。由于模式识别受体（PRR） toll样受体7 （TLR7）是病毒基因组的主要传感器，我们研究了TLR7对IAV的识别如何影响继发性肺炎球菌感染的发展。在IAV小鼠模型中，tlr7缺陷宿主诱导了强有力的抗病毒反应，并显示出不变的存活率。在急性流感期间继发性肺炎球菌感染中，TLR7ko小鼠显示出与野生型（WT）宿主相似的致命结果，尽管疾病进展明显延迟。此外，当病毒清除后发生细菌重复感染时，WT和tlr7缺陷宿主的死亡率相似，尽管我们发现从iav预感染宿主中分离的肺泡巨噬细胞在TLR7ko中比WT小鼠的吞噬活性增强。因此，我们表明，病毒感知PRR调节IAV后继发性肺炎球菌感染的进展。然而，在WT和TLR7ko宿主中，致命的总体结果表明，与tlr7触发不同的过程覆盖了这一单一PRR的贡献。
Increased risk for bacterial superinfections substantially contributes to the mortality caused by influenza A virus (IAV) epidemics. While the mechanistic basis for this lethal synergism is still insufficiently understood, immune modulation through the viral infection has been shown to be involved. Since the pattern-recognition receptor (PRR) toll-like receptor 7 (TLR7) is a major sensor for the viral genome, we studied how IAV recognition by TLR7 influences the development of secondary pneumococcal infection. In a mouse model of IAV, TLR7-deficient hosts induced a potent antiviral response and showed unchanged survival. In secondary pneumococcal infection during acute influenza, TLR7ko mice showed a fatal outcome similar to wild-type (WT) hosts, despite significantly delayed disease progression. Also, when bacterial superinfection occurred after virus clearance, WT and TLR7-deficient hosts showed similar mortality, even though we found the phagocytic activity of alveolar macrophages isolated from IAV-pre-infected hosts to be enhanced in TLR7ko over WT mice. Thus, we show that a virus-sensing PRR modulates the progression of secondary pneumococcal infection following IAV. However, the fatal overall outcome in WT as well as TLR7ko hosts suggests that processes distinct from TLR7-triggering override the contribution of this single PRR.
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影响因子：
20.3
作者：
Kamphuis, Elisabeth;Junt, Tobias;Kalinke, Ulrich
通讯作者：
Kalinke, Ulrich
[肺炎链球菌感染].
DOI：
--
发表时间：
2003
期刊：
Nihon rinsho. Japanese journal of clinical medicine
影响因子：
--
作者：
K. Tateda
通讯作者：
K. Tateda
影响因子：
4.4
作者：
Koyama, Shohei;Ishii, Ken J.;Akira, Shizuo
通讯作者：
Akira, Shizuo
影响因子：
5.3
作者：
M. Dessing;K. F. van der Sluijs;C. Spek;T. van der Poll
通讯作者：
T. van der Poll
影响因子：
30.5
作者：
Hemmi, H;Kaisho, T;Akira, S
通讯作者：
Akira, S