The Aga Khan University, Karachi, Pakistan.
PLoS One. 2009 Dec 29;4(12):e8459. doi: 10.1371/journal.pone.0008459.
Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNgamma, TNFalpha and downmodulatory IL10 play a central role in the restriction of M. tuberculosis infections, but is unclear whether these markers are indicative of tuberculosis disease severity.
We investigated live M. tuberculosis- and M. bovis BCG-induced peripheral blood mononuclear cell responses in patients with tuberculosis (TB) and healthy endemic controls (ECs, n = 36). TB patients comprised pulmonary (PTB, n = 34) and extrapulmonary groups, subdivided into those with less severe localized extrapulmonary TB (L-ETB, n = 16) or severe disseminated ETB (D-ETB, n = 16). Secretion of CCL2, IFNgamma, IL10 and CCL3, and mRNA expression of CCL2, TNFalpha, CCL3 and CXCL8 were determined.
M. tuberculosis- and BCG-induced CCL2 secretion was significantly increased in both PTB and D-ETB (p<0.05, p<0.01) as compared with L-ETB patients. CCL2 secretion in response to M. tuberculosis was significantly greater than to BCG in the PTB and D-ETB groups. M. tuberculosis-induced CCL2 mRNA transcription was greater in PTB than L-ETB (p = 0.023), while CCL2 was reduced in L-ETB as compared with D-ETB (p = 0.005) patients. M. tuberculosis-induced IFNgamma was greater in L-ETB than PTB (p = 0.04), while BCG-induced IFNgamma was greater in L-ETB as compared with D-ETB patients (p = 0.036). TNFalpha mRNA expression was raised in PTB as compared with L-ETB group in response to M. tuberculosis (p = 0.02) and BCG (p = 0.03). Mycobacterium-induced CCL3 and CXCL8 was comparable between TB groups.
The increased CCL2 and TNFalpha in PTB patients may support effective leucocyte recruitment and M. tuberculosis localization. CCL2 alone is associated with severity of TB, possibly due to increased systemic inflammation found in severe disseminated TB or due to increased monocyte infiltration to lung parenchyma in pulmonary disease.
白细胞激活趋化因子，如 CCL2、CCL3 和 CXCL8，以及前炎症性 IFNγ、TNFα 和下调性 IL10，在限制结核分枝杆菌感染方面发挥着核心作用，但这些标志物是否能指示结核病的严重程度尚不清楚。
我们研究了结核病（TB）患者和健康地方性对照（EC，n=36）中活结核分枝杆菌和牛分枝杆菌卡介苗诱导的外周血单核细胞反应。TB 患者包括肺结核（PTB，n=34）和肺外组，分为局部肺外 TB 程度较轻的组（L-ETB，n=16）或严重播散性 ETB 组（D-ETB，n=16）。测定 CCL2、IFNγ、IL10 和 CCL3 的分泌以及 CCL2、TNFα、CCL3 和 CXCL8 的 mRNA 表达。
与 L-ETB 患者相比，PTB 和 D-ETB 患者的结核分枝杆菌和卡介苗诱导的 CCL2 分泌均显著增加（p<0.05，p<0.01）。PTB 和 D-ETB 组中，结核分枝杆菌诱导的 CCL2 分泌显著高于卡介苗。结核分枝杆菌诱导的 CCL2 mRNA 转录在 PTB 中高于 L-ETB（p=0.023），而 L-ETB 中 CCL2 的表达低于 D-ETB（p=0.005）。L-ETB 中结核分枝杆菌诱导的 IFNγ高于 PTB（p=0.04），而 L-ETB 中卡介苗诱导的 IFNγ高于 D-ETB（p=0.036）。结核分枝杆菌诱导的 TNFα mRNA 表达在 PTB 中高于 L-ETB 组（p=0.02）和卡介苗（p=0.03）。TB 组之间的分枝杆菌诱导的 CCL3 和 CXCL8 相似。
PTB 患者中 CCL2 和 TNFα 的增加可能支持白细胞的有效募集和结核分枝杆菌的定位。单独的 CCL2 与结核病的严重程度有关，可能是由于严重播散性结核病中发现的全身炎症增加，也可能是由于肺疾病中单核细胞向肺实质的浸润增加。
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