Type I Interferon Orchestrates Demand-Adapted Monopoiesis during Influenza A Virus Infection via STAT1-Mediated Upregulation of Macrophage Colony-Stimulating Factor Receptor Expression.
Type I Interferon Orchestrates Demand-Adapted Monopoiesis during Influenza A Virus Infection via STAT1-Mediated Upregulation of Macrophage Colony-Stimulating Factor Receptor Expression.
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I 型干扰素在甲型流感病毒感染期间通过 STAT1 介导的巨噬细胞集落刺激因子受体表达上调来协调需求适应的单核细胞生成。
DOI：
10.1128/jvi.00102-23
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发表时间：
2023
影响因子：
5.4
通讯作者：
Tsai,Ching-Hwa
中科院分区：
文献类型：
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作者：
Lin,Sue-Jane;Lin,Kai-Min;Chen,Shi-YoJill;Ku,Chia-Chi;Huang,Chen-Wei;Huang,Chi-Hsiang;GaleJr,Michael;Tsai,Ching-Hwa
与全身感染不同，局部病毒感染是否以及如何影响骨髓中的造血系统在很大程度上是未知的。在这项研究中，我们发现甲型流感病毒（IAV）感染导致骨髓中需求适应的单核细胞生成。β干扰素（IFN-β）启动子刺激因子1 (IPS-1) I型IFN- IFN-α受体1 （IFNAR1）轴介导的信号传导可诱导粒细胞-单核细胞祖细胞（GMP）群体的紧急扩张，并通过信号转导和转录激活因子1 （STAT1）上调巨噬细胞集落刺激因子受体（M-CSFR）在双能性GMP和单核细胞祖细胞上的表达，导致粒细胞祖细胞比例缩小。为了进一步研究需求适应单产对iav诱导的继发性细菌感染的影响，研究人员用iav感染的野生型（WT）和stat1−/−小鼠感染肺炎链球菌。与WT小鼠相比，Stat1−/−小鼠没有表现出需求适应的单核细胞，有更多的浸润性粒细胞，能够有效地消除细菌感染。我们的研究结果表明，甲型流感病毒感染诱导I型干扰素（IFN）介导的紧急造血，以扩大骨髓中的GMP群体。在GMP人群中，I型IFN-STAT1轴通过上调M-CSFR表达参与介导病毒感染驱动的需求适应性垄断。由于继发性细菌感染通常在病毒感染期间出现，并可能导致严重甚至致命的临床并发症，因此我们进一步评估了观察到的单核细胞对细菌清除的影响。我们的研究结果表明，由此导致的粒细胞比例下降可能在降低iav感染宿主有效清除继发性细菌感染的能力中发挥作用。我们的研究结果不仅提供了I型IFN调节功能的更完整的图片，而且还强调需要更全面地了解局部感染期间造血功能的潜在变化，以便更好地为临床干预提供信息。
Whether and how a local virus infection affects the hematopoietic system in the bone marrow is largely unknown, unlike with systemic infection. In this study, we showed that influenza A virus (IAV) infection leads to demand-adapted monopoiesis in the bone marrow. The beta interferon (IFN-β) promoter stimulator 1 (IPS-1)–type I IFN–IFN-α receptor 1 (IFNAR1) axis-mediated signaling was found to induce the emergency expansion of the granulocyte-monocyte progenitor (GMP) population and upregulate the expression of the macrophage colony-stimulating factor receptor (M-CSFR) on bipotent GMPs and monocyte progenitors via the signal transducer and activator of transcription 1 (STAT1), leading to a scaled-back proportion of granulocyte progenitors. To further address the influence of demand-adapted monopoiesis on IAV-induced secondary bacterial infection, IAV-infected wild-type (WT) andStat1−/−mice were challenged with Streptococcus pneumoniae. Compared with WT mice,Stat1−/−mice did not demonstrate demand-adapted monopoiesis, had more infiltrating granulocytes, and were able to effectively eliminate the bacterial infection.IMPORTANCEOur findings show that influenza A virus infection induces type I interferon (IFN)-mediated emergency hematopoiesis to expand the GMP population in the bone marrow. The type I IFN-STAT1 axis was identified as being involved in mediating the viral-infection-driven demand-adapted monopoiesis by upregulating M-CSFR expression in the GMP population. As secondary bacterial infections often manifest during a viral infection and can lead to severe or even fatal clinical complications, we further assessed the impact of the observed monopoiesis on bacterial clearance. Our results suggest that the resulting decrease in the proportion of granulocytes may play a role in diminishing the IAV-infected host’s ability to effectively clear secondary bacterial infection. Our findings not only provide a more complete picture of the modulatory functions of type I IFN but also highlight the need for a more comprehensive understanding of potential changes in hematopoiesis during local infections to better inform clinical interventions.