Masumi Atsuko, Mochida Keiko, Takizawa Kazuya, Mizukami Takuo, Kuramitsu Madoka, Tsuruhara Momoka, Mori Shigetarou, Shibayama Keigo, Yamaguchi Kazunari, Hamaguchi Isao
Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.
Present address: Faculty of Pharmaceutical Sciences, Aomori University, 2-3-1, Kohbata, Aomori-shi, Aomori, 030-0943 Japan.
Inflamm Regen. 2016 Aug 26;36:21. doi: 10.1186/s41232-016-0024-3. eCollection 2016.
Bacterial infections cause an increase in the population of hematopoietic stem cells (HSCs). To investigate the downstream factors associated with hematopoietic stem cells, mice are infected with ().
() infection induces the enlargement of the spleen and changes in histopathology, including changes to the lineage populations. A dramatic expansion of Linc-kitSca-1 (KSL) cells in mouse bone marrow cells and spleen cells was detected 4 weeks after infection with ; however, there was no difference in the engraft activity between infected and un-infected mouse bone marrow cells. We tested the cytokine and cytokine-related gene expression after infection and found that IFN-γ expression increased and peaked at 4 weeks in both bone marrow and spleen cells. The expression of Sca-1 gene peaked at 4 weeks in the bone marrow but peaked at 2 weeks in spleen cells, although the Sca-1 surface marker peaked at 4 weeks after infection in both bone marrow and spleen cells. Interferon regulatory factor-2 (IRF-2) expression did not change in the bone marrow cells, whereas it decreased in spleen cells at 4 weeks and IRF-1 expression was up-regulated in both bone marrow and spleen cells after infection. However, the up-regulation of IRF-1 was not correlated with IFN-γ expression in the -infected mouse spleen cells.
This finding suggests that the IFN-γ production mediated by infection alters the population of KSL cells during host defense, and the down-regulation of the IFN-γ response in spleen cells occurs at the late stage after infection.
细菌感染会导致造血干细胞（HSCs）数量增加。为了研究与造血干细胞相关的下游因子，用（）感染小鼠。
（）感染导致脾脏肿大和组织病理学变化，包括谱系群体的变化。感染（）4周后，在小鼠骨髓细胞和脾细胞中检测到Linc-kitSca-1（KSL）细胞显著扩增；然而，感染组和未感染组小鼠骨髓细胞的植入活性没有差异。我们检测了感染（）后的细胞因子和细胞因子相关基因表达，发现骨髓和脾细胞中的IFN-γ表达均增加，并在4周时达到峰值。Sca-1基因的表达在骨髓中于4周时达到峰值，而在脾细胞中于2周时达到峰值，尽管Sca-1表面标志物在骨髓和脾细胞感染后4周时达到峰值。干扰素调节因子2（IRF-2）在骨髓细胞中的表达没有变化，而在脾细胞中于4周时下降，感染后骨髓和脾细胞中的IRF-1表达均上调。然而，在感染（）的小鼠脾细胞中，IRF-1的上调与IFN-γ表达无关。
这一发现表明，（）感染介导的IFN-γ产生在宿主防御过程中改变了KSL细胞群体，且脾细胞中IFN-γ反应的下调发生在感染（）后的晚期。
