Division of Medical Microbiology, University of Cape Town, Cape Town, South Africa.
PLoS One. 2012;7(8):e43170. doi: 10.1371/journal.pone.0043170. Epub 2012 Aug 16.
Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis.
Strains from two major modern lineages (lineage 2 [East-Asian] and lineage 4 [Euro-American]) circulating in the Western Cape in South Africa as well as a comparator modern lineage (lineage 3 [CAS/Delhi]) were identified. We assessed two virulence associated characteristics: mycobacterial growth (in liquid broth and monocyte derived macrophages) and early pro-inflammatory cytokine induction.
In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains (lineage 4 vs. lineage 2 p=0.0024; lineage 4 vs. lineage 3 p=0.0005). Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p<0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages (lineage 2: median TNF 362 pg/ml, IL-12p40 91 pg/ml; lineage 3: median TNF 1818 pg/ml, IL-12p40 123 pg/ml; lineage 4: median TNF 1207 pg/ml, IL-12p40 205 pg/ml;). In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40.
Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of these strains in different human populations.
结核分枝杆菌菌株在毒力上存在差异。在美国和英国爆发的菌株已被证明可颠覆先天免疫反应，作为潜在的免疫逃避机制。然而，关于这些免疫抑制模式是否是个别菌株的特征，或者是否是结核分枝杆菌广泛克隆谱系的特征，几乎没有信息。
鉴定了在南非西开普省流行的两个主要现代谱系（谱系 2 [东亚]和谱系 4 [欧美]）以及一个比较现代谱系（谱系 3 [CAS/德里]）的菌株。我们评估了两个与毒力相关的特征：分枝杆菌生长（在液体肉汤和单核细胞衍生的巨噬细胞中）和早期前炎症细胞因子诱导。
在液体培养中，谱系 4 菌株的生长速度比其他菌株（谱系 4 与谱系 2，p=0.0024；谱系 4 与谱系 3，p=0.0005）更快，达到更高的平台水平。谱系 3 菌株的特点是低而早的平台水平，而谱系 2 菌株表现出中间生长表型。在单核细胞衍生的巨噬细胞中，谱系 2 菌株的生长速度快于谱系 3 菌株（p<0.01），而谱系 4 菌株表现出中间表型。与其他谱系相比，谱系 2 菌株诱导的促炎 TNF 和 IL-12p40 水平最低（谱系 2：中位数 TNF 362 pg/ml，IL-12p40 91 pg/ml；谱系 3：中位数 TNF 1818 pg/ml，IL-12p40 123 pg/ml；谱系 4：中位数 TNF 1207 pg/ml，IL-12p40 205 pg/ml）。相反，谱系 4 菌株诱导高水平的 IL-12p40 和中等水平的 TNF。谱系 3 菌株诱导高水平的 TNF 和中等水平的 IL-12p40。
来自三个主要现代谱系的结核分枝杆菌菌株具有不同的生长和细胞因子诱导模式。快速生长和免疫抑制可能是这些菌株在不同人群中成功的关键特征。
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