EBioMedicine. 2015 Nov;2(11):1619-26. doi: 10.1016/j.ebiom.2015.09.027.
The ratio of monocytes and lymphocytes (ML ratio) in peripheral blood is associated with tuberculosis and malaria disease risk and cancer and cardiovascular disease outcomes. We studied anti-mycobacterial function and the transcriptome of monocytes in relation to the ML ratio. Mycobacterial growth inhibition assays of whole or sorted blood were performed and mycobacteria were enumerated by liquid culture. Transcriptomes of unstimulated CD14 + monocytes isolated by magnetic bead sorting were characterised by microarray. Transcript expression was tested for association with ML ratio calculated from leucocyte differential counts by linear regression. The ML ratio was associated with mycobacterial growth in vitro (β = 2.23, SE 0.91, p = 0.02). Using sorted monocytes and lymphocytes, in vivo ML ratio (% variance explained R(2) = 11%, p = 0.02) dominated over in vitro ratios (R(2) = 5%, p = 0.10) in explaining mycobacterial growth. Expression of 906 genes was associated with the ML ratio and 53 with monocyte count alone. ML-ratio associated genes were enriched for type-I and -II interferon signalling (p = 1.2 × 10(− 8)), and for genes under transcriptional control of IRF1, IRF2, RUNX1, RELA and ESRRB. The ML-ratio-associated gene set was enriched in TB disease (3.11-fold, 95% CI: 2.28-4.19, p = 5.7 × 10(− 12)) and other inflammatory diseases including atopy, HIV, IBD and SLE. The ML ratio is associated with distinct transcriptional and anti-mycobacterial profiles of monocytes that may explain the disease associations of the ML ratio.
外周血单核细胞与淋巴细胞比值（ML 比值）与结核病和疟疾风险以及癌症和心血管疾病结局相关。我们研究了与 ML 比值相关的抗分枝杆菌功能和单核细胞转录组。进行了全血或分选血的抗分枝杆菌生长抑制试验，并通过液体培养对分枝杆菌进行计数。通过微阵列分析了用磁珠分选分离的未刺激 CD14+单核细胞的转录组。通过线性回归测试了白细胞差异计数计算的 ML 比值与转录表达的相关性。ML 比值与体外分枝杆菌生长相关（β=2.23，SE 0.91，p=0.02）。使用分选的单核细胞和淋巴细胞，体内 ML 比值（%解释方差 R2=11%，p=0.02）比体外比值（R2=5%，p=0.10）更能解释分枝杆菌生长。有 906 个基因的表达与 ML 比值相关，53 个基因与单核细胞计数单独相关。与 ML 比值相关的基因富集了 I 型和 II 型干扰素信号（p=1.2×10−8），以及受 IRF1、IRF2、RUNX1、RELA 和 ESRRB 转录控制的基因。ML 比值相关基因集在结核病（3.11 倍，95%CI：2.28-4.19，p=5.7×10−12）和其他炎症性疾病中富集，包括过敏、HIV、IBD 和 SLE。ML 比值与单核细胞的独特转录和抗分枝杆菌特征相关，这可能解释了 ML 比值与疾病的关联。
