Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, London, UK.
Nat Immunol. 2010 Jun;11(6):477-85. doi: 10.1038/ni.1869. Epub 2010 May 2.
Although the relationship between hematopoietic stem cells and progenitor populations has been investigated extensively under steady-state conditions, the dynamic response of the hematopoietic compartment during acute infection is largely unknown. Here we show that after infection of mice with Plasmodium chabaudi, a c-Kit(hi) progenitor subset positive for interleukin 7 receptor-alpha (IL-7Ralpha) emerged that had both lymphoid and myeloid potential in vitro. After being transferred into uninfected alymphoid or malaria-infected hosts, IL-7Ralpha(+)c-Kit(hi) progenitors generated mainly myeloid cells that contributed to the clearance of infected erythrocytes in infected hosts. The generation of these infection-induced progenitors was critically dependent on interferon-gamma (IFN-gamma) signaling in hematopoietic progenitors. Thus, IFN-gamma is a key modulator of hematopoiesis and innate and adaptive immunity during acute malaria infection.
尽管在稳态条件下已经广泛研究了造血干细胞和祖细胞群体之间的关系,但在急性感染期间造血部分的动态反应在很大程度上是未知的。在这里,我们表明,在感染疟原虫后,出现了一个 c-Kit(hi)祖细胞亚群,该亚群对白细胞介素 7 受体-α (IL-7Ralpha)呈阳性,具有体外淋巴样和骨髓样潜能。在转移到未感染的无淋巴细胞或疟疾感染的宿主后,IL-7Ralpha(+)c-Kit(hi)祖细胞主要产生有助于清除感染红细胞的骨髓细胞。这些感染诱导的祖细胞的产生在造血祖细胞中的干扰素-γ (IFN-γ)信号传导中是至关重要的。因此,IFN-γ是急性疟疾感染期间造血和先天及适应性免疫的关键调节剂。