Mizrachi-Nebenzahl Y, Lifshitz S, Teitelbaum R, Novick S, Levi A, Benharroch D, Ling E, Dagan R
Ben Gurion University of the Negev, Soroka University Medical Center, Beer-Sheva, Israel.
Clin Exp Immunol. 2003 Oct;134(1):23-31. doi: 10.1046/j.1365-2249.2003.02261.x.
Streptococcus pneumoniae infection may result in asymptomatic carriage, mucosal or invasive disease. We hypothesize that self-limiting or fatal disease outcome follows infection with S. pneumoniae differential activation of the host immune response. BALB/c and C57BL/6 mice were inoculated intranasally with S. pneumoniae serotype 3 strain WU2 and serotype 14 strain DW14 and mortality, bacterial load, pathological changes in the lungs and cytokines mRNA levels in the spleen were analysed. No differences between the C57BL/6 and the BALB/c inbred mice were observed except for the severity of their lung pathology and IL-4 expression. Infection of the two mouse strains with S. pneumoniae WU2 resulted in sepsis and death that occurred within 4 days post-inoculation. This death was preceded, in both mouse strains, in an increase over time of the lung bacterial load and bacteraemia. The lung pathology was characterized by diffuse pneumonia with marked congestion of the lungs. Analysis of mRNA expression of cytokines in the spleen revealed no alterations in tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-12 and interferon (IFN)-gamma and induction of IL-10 and IL-4. The two strains of mice survived infection with S. pneumoniae DW14. This was accompanied by a reduction over time of lung bacterial load and bacteraemia. The lung pathology was characterized by focal lymphocyte infiltration and preserved architecture of the organ. Analysis of mRNA expression of cytokines in the spleen revealed a significant decrease in the levels of TNF-alpha, TGF-beta, IL-12 and IFN-gamma mRNA expression, which usually precedes cytokine protein expression. Interestingly, a significant increase in the levels of IL-4 mRNA expression was found in BALB/c mice only. This study suggests that differential activation or evasion of cytokine expression by S. pneumoniae virulent strains determines disease outcome regardless of the host's immunogenetic background.
肺炎链球菌感染可能导致无症状携带、黏膜疾病或侵袭性疾病。我们推测，宿主免疫反应的差异激活导致了肺炎链球菌感染后自限性或致命性疾病的结果。将BALB/c和C57BL/6小鼠经鼻接种肺炎链球菌3型菌株WU2和14型菌株DW14，并分析死亡率、细菌载量、肺部病理变化以及脾脏中细胞因子mRNA水平。除了肺部病理严重程度和白细胞介素-4（IL-4）表达外，未观察到C57BL/6和BALB/c近交系小鼠之间存在差异。用肺炎链球菌WU2感染这两种小鼠品系均导致败血症和死亡，死亡发生在接种后4天内。在这两种小鼠品系中，死亡之前肺部细菌载量和菌血症均随时间增加。肺部病理特征为弥漫性肺炎伴肺部明显充血。对脾脏中细胞因子mRNA表达的分析显示，肿瘤坏死因子（TNF）-α、转化生长因子（TGF）-β、白细胞介素（IL）-12和干扰素（IFN）-γ无变化，而IL-10和IL-4被诱导。这两种小鼠品系在感染肺炎链球菌DW14后存活。这伴随着肺部细菌载量和菌血症随时间减少。肺部病理特征为局灶性淋巴细胞浸润且器官结构保留。对脾脏中细胞因子mRNA表达的分析显示，TNF-α、TGF-β、IL-12和IFN-γ mRNA表达水平显著降低，这通常先于细胞因子蛋白表达。有趣的是，仅在BALB/c小鼠中发现IL-4 mRNA表达水平显著增加。这项研究表明，肺炎链球菌毒力菌株对细胞因子表达的差异激活或逃避决定了疾病结果，而与宿主的免疫遗传背景无关。
