Microbial and Molecular Pathogenesis, Texas A&M Health Science Center, College Station, TX 77843-1114, USA.
Immunology. 2009 Sep;128(1 Suppl):e296-305. doi: 10.1111/j.1365-2567.2008.02962.x. Epub 2008 Nov 7.
Cytokine messenger RNA (mRNA) expression was investigated in the spleen and lung digest cells of bacillus Calmette-Guérin (BCG)-vaccinated and non-vaccinated guinea pigs following low-dose, pulmonary exposure to virulent Mycobacterium tuberculosis. After purified protein derivative (PPD) stimulation, the levels of lung cell interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and spleen cell interleukin-12 (IL-12) p40 mRNAs were significantly increased in the non-vaccinated M. tuberculosis-infected guinea pigs compared to the BCG-vaccinated guinea pigs. In contrast, the expression of anti-inflammatory transforming growth factor-beta and IL-10 mRNAs was significantly enhanced in the spleens of BCG-vaccinated animals. Despite the presence of protective cytokine mRNA expression, the non-vaccinated guinea pigs had significantly higher lung and spleen bacterial burdens. In contrast, BCG-vaccinated guinea pigs controlled the bacterial multiplication in their lungs and spleens, indicating that both protective as well as anti-inflammatory cytokine responses are associated with a reduction in bacteria. In addition, lung digest cells from non-vaccinated guinea pigs contained a significantly higher percentage of neutrophils, CD3(+) and CD8(+) T cells, while the percentage of macrophages was increased in the BCG-vaccinated animals. Total and purified lung digest T cells co-cultured with lung macrophages (LMøs) proliferated poorly after PPD stimulation in both non-vaccinated and BCG-vaccinated animals while robust proliferation to PPD was observed when T cells were co-cultured with peritoneal macrophages (PMøs). Macrophages within the lung compartment appear to regulate the response of T cells irrespective of the vaccination status in guinea pigs. Taken together, our results suggest that type I cytokine mRNA expression is not associated with vaccine-induced protection in the low-dose guinea pig model of tuberculosis.
卡介苗（BCG）接种和未接种豚鼠经低剂量肺部暴露于有毒结核分枝杆菌后，研究了其脾脏和肺部消化细胞中的细胞因子信使 RNA（mRNA）表达。经纯化蛋白衍生物（PPD）刺激后，与 BCG 接种的豚鼠相比，未接种的结核分枝杆菌感染豚鼠的肺部细胞干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和脾脏细胞白细胞介素-12（IL-12）p40mRNA 的水平显著升高。相比之下，BCG 接种动物的脾脏中抗炎转化生长因子-β和 IL-10mRNA 的表达显著增强。尽管存在保护性细胞因子 mRNA 表达，但未接种豚鼠的肺部和脾脏细菌负荷明显更高。相比之下，BCG 接种豚鼠控制了肺部和脾脏的细菌繁殖，表明保护性和抗炎性细胞因子反应均与减少细菌有关。此外，未接种豚鼠的肺部消化细胞中中性粒细胞、CD3(+)和 CD8(+)T 细胞的百分比显著升高，而 BCG 接种动物的巨噬细胞百分比增加。未接种和 BCG 接种豚鼠的总肺消化 T 细胞与肺巨噬细胞（LMøs）共培养后，经 PPD 刺激时增殖不良，而当 T 细胞与腹腔巨噬细胞（PMøs）共培养时，对 PPD 则表现出强烈的增殖反应。肺内巨噬细胞似乎调节了 T 细胞的反应，而与豚鼠的接种状态无关。总之，我们的研究结果表明，I 型细胞因子 mRNA 表达与低剂量豚鼠结核模型中的疫苗诱导保护无关。
