Peterson V M, Madonna G S, Vogel S N
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889-5145.
Infect Immun. 1992 Apr;60(4):1375-84. doi: 10.1128/iai.60.4.1375-1384.1992.
Inheritance of the Ityr or the Itys allele of the Ity murine gene confers resistance or increased susceptibility, respectively, to Salmonella typhimurium infection. Recent studies have documented that Ity gene expression may determine net intracellular replication of S. typhimurium by modulating macrophage function. The purpose of this study was to determine if Ity gene expression modulated macrophage stem cell proliferation as well. To detect possible Ity-associated alterations in macrophage stem cell proliferation during endotoxin challenge or S. typhimurium infection, the congenic strain pair BALB/c (Itys) and C.D2-Idh-1, Pep-3 N20F8 (Ityr) were injected intraperitoneally with 25 micrograms of bacterial lipopolysaccharide (LPS) or approximately 10(3) S. typhimurium, and myelopoiesis was evaluated. At 72 h after LPS injection, both BALB/c and C.D2 mice developed comparable degrees of bone marrow hypocellularity and splenomegaly, and cell sizing profiles indicated a normal response to a single injection of LPS in both strains of mice. Although an inhibitor to colony-stimulating factor activity was detected in the sera and plasma of C.D2 mice, the number of myeloid stem cells cultured from the bone marrow and spleen of each mouse strain were comparable. S. typhimurium infection resulted in earlier symptoms, a larger bacterial load, a higher mortality rate, and a greater bone marrow hypocellularity and splenomegaly in BALB/c mice compared with those in C.D2 mice. Despite a dramatic increase in bacterial load, a decrease in both bone marrow and splenic myeloid stem cell numbers was noted in BALB/c mice, while stem cell numbers remained constant in C.D2 mice between days 3 and 5 and increased dramatically at day 7 after infection. These data suggest that BALB/c and C.D2 mice may exhibit a divergent myelopoietic response to S. typhimurium infection. It appears that a paradoxical failure of myelopoiesis in Itys mice during S. typhimurium infection may contribute to the observed increase in mortality.
Ity小鼠基因的Ityr或Itys等位基因的遗传分别赋予对鼠伤寒沙门氏菌感染的抗性或易感性增加。最近的研究表明，Ity基因表达可能通过调节巨噬细胞功能来决定鼠伤寒沙门氏菌在细胞内的净复制。本研究的目的是确定Ity基因表达是否也调节巨噬细胞干细胞增殖。为了检测在内毒素攻击或鼠伤寒沙门氏菌感染期间巨噬细胞干细胞增殖中可能与Ity相关的改变，将同基因品系对BALB/c（Itys）和C.D2-Idh-1、Pep-3 N20F8（Ityr）腹腔注射25微克细菌脂多糖（LPS）或约10³个鼠伤寒沙门氏菌，并评估骨髓生成。在注射LPS后72小时，BALB/c和C.D2小鼠均出现了相当程度的骨髓细胞减少和脾肿大，细胞大小分布表明两种品系小鼠对单次注射LPS的反应正常。尽管在C.D2小鼠的血清和血浆中检测到集落刺激因子活性的抑制剂，但从每个小鼠品系的骨髓和脾脏中培养的髓系干细胞数量相当。与C.D2小鼠相比，鼠伤寒沙门氏菌感染导致BALB/c小鼠出现更早的症状、更大的细菌载量、更高的死亡率以及更严重的骨髓细胞减少和脾肿大。尽管细菌载量急剧增加，但BALB/c小鼠的骨髓和脾脏髓系干细胞数量均减少，而C.D2小鼠的干细胞数量在感染后第3天至第5天保持恒定，并在第7天急剧增加。这些数据表明，BALB/c和C.D2小鼠对鼠伤寒沙门氏菌感染可能表现出不同的骨髓生成反应。在鼠伤寒沙门氏菌感染期间，Itys小鼠骨髓生成出现矛盾性失败似乎可能导致观察到的死亡率增加。
