CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
CCL2 responses to Mycobacterium tuberculosis are associated with disease severity in tuberculosis.
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CCL2对结核分枝杆菌的反应与结核病中的疾病严重程度有关。
DOI：
10.1371/journal.pone.0008459
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发表时间：
2009-12-29
期刊：
影响因子：
3.7
通讯作者：
Hussain R
中科院分区：
文献类型：
--
作者：
Hasan Z;Cliff JM;Dockrell HM;Jamil B;Irfan M;Ashraf M;Hussain R
白细胞激活趋化因子如CCL2、CCL3和CXCL8与促炎IFNγ、TNFα和下调IL10在限制结核分枝杆菌感染中发挥核心作用，但尚不清楚这些标志物是否指示结核病的严重程度。我们研究了结核（TB）患者和健康地方性对照（ECs, n = 36）中活的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。结核病患者分为肺（PTB, n = 34）和肺外组，再细分为轻度局限性肺外结核（L-ETB, n = 16）和重度弥散性ETB （D-ETB, n = 16）。检测CCL2、IFNγ、IL10和CCL3的分泌，以及CCL2、TNFα、CCL3和CXCL8 mRNA的表达。与L-ETB患者相比，结核分枝杆菌和卡介苗诱导的PTB和D-ETB患者CCL2分泌显著增加（p<0.05, p<0.01）。PTB组和D-ETB组CCL2分泌量明显高于BCG。结核分枝杆菌诱导的CCL2 mRNA转录在PTB中高于L-ETB (p = 0.023)，而CCL2在L-ETB中低于D-ETB （p = 0.005）。结核分枝杆菌诱导的IFNγ在L-ETB中高于PTB (p = 0.04)，而bcg诱导的IFNγ在L-ETB中高于D-ETB （p = 0.036）。结核分枝杆菌（M. tuberculosis, p = 0.02）和卡介苗（BCG, p = 0.03）对结核分枝杆菌（M. tuberculosis, p = 0.02）和结核分枝杆菌（L-ETB）对结核分枝杆菌（M. tuberculosis, p = 0.03）治疗后，PTB组织中TNFα mRNA表达升高。结核分枝杆菌诱导的CCL3和CXCL8在结核组间具有可比性。PTB患者CCL2和TNFα升高可能支持有效的白细胞募集和结核分枝杆菌定位。CCL2单独与结核病的严重程度相关，可能是由于在严重弥散性结核病中发现全身性炎症增加，或由于肺部疾病中单核细胞浸润到肺实质增加。
Leucocyte activating chemokines such as CCL2, CCL3, and CXCL8 together with proinflammatory IFNγ, TNFα 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, IFNγ, IL10 and CCL3, and mRNA expression of CCL2, TNFα, 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 IFNγ was greater in L-ETB than PTB (p = 0.04), while BCG-induced IFNγ was greater in L-ETB as compared with D-ETB patients (p = 0.036). TNFα 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 TNFα 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.
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影响因子：
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作者：
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