Nishikawa F, Yoshikawa S, Harada H, Kita M, Kita E
Department of Bacteriology, Nara Medical University, Nara, Japan.
Immunology. 1998 Dec;95(4):640-7. doi: 10.1046/j.1365-2567.1998.00647.x.
Our previous study has shown that the rapid and sufficient activation of complement by Salmonella lipopolysaccharide occurs in genetically resistant (Ityr) A/J mice. To assess whether the level of complement activation by a virulent strain of Salmonella typhimurium regulates the level of murine natural resistance, we compared levels of serum complement activation by S. typhimurium and kinetics of serum-opsonized S. typhimurium grown in macrophages using several strains of resistant (Ityr) and susceptible (Itys) mice. Itys macrophages killed intracellular S. typhimurium to the same extent as did Ityr macrophages when the pathogen was opsonized with Ityr serum. Opsonization of S. typhimurium with Itys serum reduced intracellular killing activity in Ityr macrophages to the same level as seen with Itys macrophages. Incubation of S. typhimurium with 25% Mg2+ EGTA (5 mm MgCl2-3 mm ethylene glycol-bis (beta-aminotheyl either)-N,N,N',N'-tetraacetic acid)-chelated Ityr serum resulted in higher levels of C3 deposition onto the surface of this bacteria, C3b generation and also C3 consumption, compared with that with Mg2+ EGTA-chelated Itys serum. Opsonization of S. typhimurium with A/J serum prior to infection increased early resistance in Itys mice. Infection with a virulent strain of S. typhimurium induced the expression of interleukin-10 (IL-10) mRNA at higher levels in C57BL/6 mice than in A/J mice. However, opsonization of S. typhimurium with A/J serum decreased bacterial growth in the spleen of C57BL/6 mice to the same level as observed for A/J mice in association with decreased expression levels of IL-10 mRNA. Moreover, administration of anti-C3 antibodies reduced the resistance of A/J mice in association with a decrease in serum levels of C3. These results indicate that the high level of complement activation via the alternative pathway in Ityr serum by a virulent strain of S. typhimurium reduces the virulence of this pathogen, which may contribute to the full expression of Ity phenotype in Ityr mice.
我们之前的研究表明，沙门氏菌脂多糖能在基因抗性（Ityr）的A/J小鼠中快速且充分地激活补体。为了评估鼠伤寒沙门氏菌强毒株激活补体的水平是否调节小鼠天然抗性水平，我们使用几种抗性（Ityr）和易感（Itys）小鼠品系，比较了鼠伤寒沙门氏菌激活血清补体的水平以及在巨噬细胞中生长的血清调理的鼠伤寒沙门氏菌的动力学。当病原体用Ityr血清调理时，Itys巨噬细胞杀死细胞内鼠伤寒沙门氏菌的程度与Ityr巨噬细胞相同。用Itys血清调理鼠伤寒沙门氏菌可使Ityr巨噬细胞内的杀伤活性降低至与Itys巨噬细胞相同的水平。与用Mg2 + EGTA（5 mM MgCl2 - 3 mM乙二醇双（β - 氨基乙基醚）- N，N，N'，N'-四乙酸）螯合的Itys血清相比，用其螯合的Ityr血清孵育鼠伤寒沙门氏菌会导致更高水平的C3沉积在该细菌表面、C3b生成以及C3消耗。感染前用A/J血清调理鼠伤寒沙门氏菌可增加Itys小鼠的早期抗性。用鼠伤寒沙门氏菌强毒株感染诱导C57BL/6小鼠中白细胞介素-10（IL-10）mRNA的表达水平高于A/J小鼠。然而，用A/J血清调理鼠伤寒沙门氏菌可使C57BL/6小鼠脾脏中的细菌生长降低至与A/J小鼠观察到的相同水平，同时IL-10 mRNA表达水平降低。此外，给予抗C3抗体可降低A/J小鼠的抗性，同时血清C3水平降低。这些结果表明，鼠伤寒沙门氏菌强毒株通过替代途径在Ityr血清中高水平激活补体可降低该病原体的毒力，这可能有助于Ityr小鼠中Ity表型的充分表达。
