Macrophages play a significant role in preventing infection through antimicrobial activities, particularly acidification, and proteolysis. Mycobacterium tuberculosis (Mtb) infection can lead to diverse outcomes, from latent asymptomatic infection to active disease involving multiple organs. Monocyte-derived macrophage is one of the main cell types accumulating in lungs following Mtb infection. The variation of intracellular activities of monocyte-derived macrophages in humans and the influence of these activities on the tuberculosis (TB) spectrum are not well understood. By exploiting ligand-specific bead-based assays, we investigated macrophage antimicrobial activities real-time in healthy volunteers (n = 53) with 35 cases of latent TB (LTB), and those with active TB (ATB), and either pulmonary TB (PTB, n = 70) or TB meningitis (TBM, n = 77). We found wide person-to-person variations in acidification and proteolytic activities in response to both non-immunogenic IgG and pathogenic ligands comprising trehalose 6,6'−dimycolate (TDM) from Mtb or β-glucan from Saccharamyces cerevisiase. The variation in the macrophage activities remained similar regardless of stimuli; however, IgG induced stronger acidification activity than immunogenic ligands TDM (P = 10⁻⁵, 3 × 10⁻⁵ and 0.01 at 30, 60, and 90 min) and β-glucan (P = 10⁻⁴, 3 × 10⁻⁴ and 0.04 at 30, 60, and 90 min). Variation in proteolysis activity was slightly higher in LTB than in ATB (CV = 40% in LTB vs. 29% in ATB, P = 0.03). There was no difference in measured antimicrobial activities in response to TDM and bacterial killing in macrophages from LTB and ATB, or from PTB and TBM. Our results indicate that antimicrobial activities of monocyte-derived macrophages vary among individuals and show immunological dependence, but suggest these activities cannot be solely responsible for the control of bacterial replication or dissemination in TB.

巨噬细胞在通过抗菌活性（尤其是酸化作用和蛋白水解作用）预防感染中起着重要作用。 结核分枝杆菌（Mtb）从潜在的无症状感染到涉及多个器官的活动性疾病，感染可能导致多种结果。单核细胞衍生的巨噬细胞是继肺后在肺中积累的主要细胞类型之一山地车感染。人们对单核细胞衍生的巨噬细胞的细胞内活性的变化以及这些活性对结核（TB）谱的影响尚不十分了解。通过利用基于配体特异性珠的检测方法，我们实时调查了健康志愿者中的巨噬细胞抗菌活性（ñ = 53），其中包括35例潜伏性结核（LTB），活动性结核（ATB）和肺结核（PTB）， ñ = 70）或结核性脑膜炎（TBM， ñ= 77）。我们发现非免疫原性IgG和包含海藻糖6,6'-的致病性配体对人的酸化和蛋白水解活性的差异很大二甲油酸酯 （TDM）来自 山地车 或来自的β-葡聚糖 酿酒酵母。无论刺激如何，巨噬细胞活性的变化均保持相似。但是，IgG诱导的酸化活性比免疫原性配体TDM（P= 10 ^-5，3 ×10 ^-5和0.01在30、60和90分钟时）和β-葡聚糖（P在30、60和90分钟时= 10 ^-4，3 ×10 ^-4和0.04）。LTB的蛋白水解活性变化略高于ATB（CV = LTB为40％，而ATB为29％，P= 0.03）。在LTB和ATB或PTB和TBM的巨噬细胞中，对TDM和细菌杀灭的抗微生物活性测定值没有差异。我们的结果表明，单核细胞衍生的巨噬细胞的抗菌活性因人而异，并显示出免疫学依赖性，但表明这些活性不能完全负责细菌在结核病中的复制或传播。