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首页> 外文期刊>Infection and immunity >MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection
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MyD88-Dependent Recruitment of Monocytes and Dendritic Cells Required for Protection from Pulmonary Burkholderia mallei Infection

机译：MyD88依赖招募保护免受肺伯克霍尔德氏菌感染的单核细胞和树突状细胞

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The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effector cells, and cytokines required for protection from respiratory B. mallei infection. We found that MyD88?/? mice were highly susceptible to pulmonary challenge with B. mallei and had significantly short survival times, increased bacterial burdens, and severe organ pathology compared to wild-type mice. Notably, MyD88?/? mice had significantly fewer monocytes and dendritic cells (DCs) in lung tissues and airways than infected wild-type mice despite markedly higher bacterial burdens. The MyD88?/? mice were also completely unable to produce gamma interferon (IFN-γ) at any time points following infection. In wild-type mice, NK cells were the primary cells producing IFN-γ in the lungs following B. mallei infection, while DCs and monocytes were the primary cellular sources of interleukin-12 (IL-12) production. Treatment with recombinant IFN-γ (rIFN-γ) was able to significantly restore protective immunity in MyD88?/? mice. Thus, we conclude that the MyD88-dependent recruitment of inflammatory monocytes and DCs to the lungs and the local production of IL-12, followed by NK cell production of IFN-γ, are the key initial cellular responses required for early protection from B. mallei infection.
机译：革兰氏阴性细菌马氏伯克霍尔德氏菌经吸入感染后会在马和人类中迅速致死，也有可能被用作生物武器。但是，关于产生保护免受肺炎双歧杆菌感染所需的早期先天免疫应答和信号传导机制知之甚少。我们以前表明单核细胞趋化蛋白1（MCP-1）是保护免受肺炎双歧杆菌感染所必需的关键趋化因子。现在，我们已经扩大了这些研究的范围，以识别关键的Toll样受体（TLR）信号传导途径，效应细胞和保护免受呼吸道双歧杆菌感染所需的细胞因子。我们发现MyD88 ？/？小鼠对野生双歧杆菌高度敏感，与野生型小鼠相比，存活时间短，细菌负担增加，器官病理严重，对小鼠的肺部挑战非常敏感。值得注意的是，尽管细菌负担明显增加，但MyD88 α/？小鼠的肺组织和气道中的单核细胞和树突状细胞（DC）明显少于受感染的野生型小鼠。 MyD88 ？/？小鼠在感染后的任何时间点也完全不能产生γ-干扰素（IFN-γ）。在野生型小鼠中，NK细胞是B. Mallei感染后在肺中产生IFN-γ的主要细胞，而DC和单核细胞是白介素12（IL-12）产生的主要细胞来源。重组IFN-γ（rIFN-γ）处理能够显着恢复MyD88 ？/？小鼠的保护性免疫。因此，我们得出结论，炎性单核细胞和DC依赖MyD88募集到肺部以及IL-12的局部产生，然后是NK细胞产生的IFN-γ，是早期预防B感染所需的关键初始细胞应答。马雷感染。

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