Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-γ signaling.
Infection-induced myelopoiesis during intracellular bacterial infection is critically dependent upon IFN-γ signaling.
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DOI：
10.4049/jimmunol.1001893
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发表时间：
2011-01-15
期刊：
影响因子：
--
通讯作者：
Winslow GM
中科院分区：
文献类型：
--
作者：
MacNamara KC;Oduro K;Martin O;Jones DD;McLaughlin M;Choi K;Borjesson DL;Winslow GM
尽管微生物感染可以改变稳定状态的造血，但驱动这种变化的机制还不是很清楚。我们讨论了干扰素-γ信号在感染诱导的骨髓抑制和人类单核细胞埃立克体病小鼠模型中的作用。人单核细胞埃立克体病是一种新出现的扁虱传播疾病。在感染Ehrlicia Muris的C57BL/6小鼠的骨髓中，我们观察到髓系祖细胞减少，正如表型和功能所定义的那样。感染的小鼠表现出伴随的骨髓内发育的髓系细胞的增加，循环单核细胞频率的增加，以及脾髓系细胞的增加。感染诱导的祖细胞表型的改变严重依赖于干扰素-γ信号，而不是干扰素-α信号。在干扰素-γ信号通路缺陷的小鼠中，我们观察到骨髓中髓系祖细胞和CD11blGr110早幼粒细胞增加，成熟粒细胞和单核细胞减少。此外，感染小鼠干扰素-γR缺陷的小鼠没有表现出贫血或循环中单核细胞的增加，它们死于感染。基因转录研究表明，小鼠感染干扰素-γR缺陷的CDllbloGr1lo早幼粒细胞中，调节粒细胞和单核细胞分化的关键转录因子Irf-1和Irf-8的表达显著降低。最后，使用混合骨髓嵌合小鼠，我们证明了干扰素-γ依赖的感染诱导的骨髓生成是通过细胞因子对发育中的髓系细胞的直接作用而发生的。我们认为，除了其许多已知的作用外，干扰素-γ还通过直接促进有助于宿主防御的髓系细胞的分化来控制感染。
Although microbial infections can alter steady-state hematopoiesis, the mechanisms that drive such changes are not well understood. We addressed a role for IFN-γ signaling in infection-induced bone marrow suppression and anemia in a murine model of human monocytic ehrlichiosis, an emerging tick-borne disease. Within the bone marrow of Ehrlichia muris-infected C57BL/6 mice, we observed a reduction in myeloid progenitor cells, as defined both phenotypically and functionally. Infected mice exhibited a concomitant increase in developing myeloid cells within the bone marrow, an increase in the frequency of circulating monocytes, and an increase in splenic myeloid cells. The infection-induced changes in progenitor cell phenotype were critically dependent on IFN-γ, but not IFN-α, signaling. In mice deficient in the IFN-γ signaling pathway, we observed an increase in myeloid progenitor cells and CDllbloGr1lo promyelocytic cells within the bone marrow, as well as reduced frequencies of mature granulocytes and monocytes. Furthermore, E. muris-infected IFN-γR–deficient mice did not exhibit anemia or an increase in circulating monocytes, and they succumbed to infection. Gene transcription studies revealed that IFN-γR–deficient CDllbloGr1lo promyelocytes from E. muris-infected mice exhibited significantly reduced expression of irf-1 and irf-8, both key transcription factors that regulate the differentiation of granulocytes and monocytes. Finally, using mixed bone marrow chimeric mice, we show that IFN-γ–dependent infection-induced myelopoiesis occurs via the direct effect of the cytokine on developing myeloid cells. We propose that, in addition to its many other known roles, IFN-γ acts to control infection by directly promoting the differentiation of myeloid cells that contribute to host defense.
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影响因子：
3.1
作者：
MacNamara, Katherine C.;Racine, Rachael;Winslow, Gary M.
通讯作者：
Winslow, Gary M.
DOI：
10.4049/jimmunol.0900612
发表时间：
2009-08-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Serbina NV;Hohl TM;Cherny M;Pamer EG
通讯作者：
Pamer EG
DOI：
10.4049/jimmunol.0800680
发表时间：
2009-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Marquis JF;LaCourse R;Ryan L;North RJ;Gros P
通讯作者：
Gros P
影响因子：
6
作者：
Olano, JP;Wen, G;Walker, DH
通讯作者：
Walker, DH
影响因子：
20.3
作者：
Selleri, C;Maciejewski, JP;Young, NS
通讯作者：
Young, NS