Cutting Edge: LPS-Induced Emergency Myelopoiesis Depends on TLR4-Expressing Nonhematopoietic Cells
Cutting Edge: LPS-Induced Emergency Myelopoiesis Depends on TLR4-Expressing Nonhematopoietic Cells
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DOI：
10.4049/jimmunol.1103253
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发表时间：
2012-06-15
影响因子：
4.4
通讯作者：
Manz, Markus G.
中科院分区：
文献类型：
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作者：
Boettcher, Steffen;Ziegler, Patrick;Manz, Markus G.
全身性细菌感染被迅速识别为一种紧急状态，导致中性粒细胞释放到循环中并增加骨髓内骨髓细胞的产生。然而，感知感染和随后转化为紧急骨髓形成的机制尚未明确。在这项研究中，我们在小鼠体内证明，令人惊讶的是，造血室中选择性TLR4表达不能诱导lps驱动的紧急骨髓生成。相反，表达tlr4的非造血细胞对于lps诱导的、g - csf介导的骨髓生成反应是必不可少的。此外，lps诱导的紧急髓细胞生成独立于完整的IL-1RI信号，因此不需要炎性体激活。总的来说，我们的研究结果揭示了非造血室病原体感知的关键和非冗余作用，该作用随后转化为细胞因子释放，以增强需求适应的骨髓细胞生产。中华免疫学杂志，2012,18(8):524 - 528。
Systemic bacterial infection is rapidly recognized as an emergency state leading to neutrophil release into the circulation and increased myeloid cell production within the bone marrow. However, the mechanisms of sensing infection and subsequent translation into emergency myelopoiesis have not been defined. In this study, we demonstrate in vivo in mice that, surprisingly, selective TLR4 expression within the hematopoietic compartment fails to induce LPS-driven emergency myelopoiesis. In contrast, TLR4-expressing nonhematopoietic cells are indispensable for LPS-induced, G-CSF-mediated myelopoietic responses. Furthermore, LPS-induced emergency myelopoiesis is independent of intact IL-1RI signaling and, thus, does not require inflammasome activation. Collectively, our findings reveal a key and nonredundant role for nonhematopoietic compartment pathogen sensing that is subsequently translated into cytokine release for enhanced, demand-adapted myeloid cell production. The Journal of Immunology, 2012, 188: 5824-5828.