Infection with Anaplasma phagocytophilum Induces Multilineage Alterations in Hematopoietic Progenitor Cells and Peripheral Blood Cells
Infection with Anaplasma phagocytophilum Induces Multilineage Alterations in Hematopoietic Progenitor Cells and Peripheral Blood Cells
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DOI：
10.1128/iai.00570-09
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Borjesson, D. L.
中科院分区：
文献类型：
--
作者：
Johns, J. L.;MacNamara, K. C.;Borjesson, D. L.
巨噬细胞无形体是一种革兰氏阴性、脂多糖(LPS)阴性的细胞内专性细菌，感染后可导致多发性外周血细胞减少症。我们假设，感染这种微生物会导致骨髓(BM)功能下降，造血祖细胞(HPC)和血统承诺细胞在已建立的感染小鼠模型中发生转移。在急性感染期间，骨髓和脾中计数了造血祖细胞和血统祖细胞。检测BM细胞因子产生和BM CXCL12表达。感染导致外周血双核细胞减少，骨髓中定向造血干细胞数量显著减少，而脾中定向定向造血干细胞数量同时增加，以及混合的、以骨髓抑制为主的骨髓细胞因子环境。骨髓细胞中CXCL12的表达显著下调，这可能是观察到的HPC转运变化的部分原因。在没有直接感染BM细胞的情况下发生了变化。造血谱系评估表明，随着粒细胞的增加，骨髓中的红细胞和B淋巴细胞丢失。这些改变伴随着淋巴组织增生引起的脾肿大和造血量增加，最显著的是红血球生成。这些变化在很大程度上模拟了骨髓和脾的炎症和内毒素介导的效应；然而，外周血中性粒细胞的数量似乎是独立调节的，因为粒细胞增殖不会导致中性粒细胞增多。我们的发现强调了一系列保守的事件，我们证明了在没有内毒素介导的急性促炎反应的情况下，内毒素阴性病原体可以引发这些事件。
Infection with Anaplasma phagocytophilum, a gram-negative, lipopolysaccharide (LPS)-negative, obligate intracellular bacterium, results in multiple peripheral blood cytopenias. We hypothesized that infection with this organism would result in decreased bone marrow ( BM) function and shifts in hematopoietic progenitor cells (HPCs) and lineage-committed cells in a well-established murine model of infection. HPCs and lineage-committed progenitors were enumerated in the BM and spleen during acute infection. BM cytokine production and BM CXCL12 expression were determined. Infection resulted in peripheral blood bicytopenia, marked decreases in the number of lineage-committed HPCs in the BM along with concurrent increases in the number of lineage-committed HPCs in the spleen, and a mixed, predominantly myelosuppressive BM cytokine environment. There was significant downregulation of CXCL12 in BM cells that may have been partially responsible for changes in HPC trafficking observed. Changes occurred in the absence of direct pathogen infection of BM cells. Hematopoietic lineage assessment demonstrated that there was loss of erythrocytes and B lymphocytes from the BM along with increased granulopoiesis. These changes were accompanied by splenomegaly due to lymphoid hyperplasia and increased hematopoiesis, most notably erythropoiesis. These changes largely mimic well-described inflammation and endotoxin-mediated effects on the BM and spleen; however, the numbers of peripheral blood neutrophils appear to be independently modulated as granulocytic hyperplasia does not result in neutrophilia. Our findings highlight a well-conserved series of events that we demonstrate can be instigated by an LPS-negative pathogen in the absence of an endotoxin-mediated acute proinflammatory response.