Table_1_Macrophage susceptibility to infection by Ghanaian Mycobacterium tuberculosis complex lineages 4 and 5 varies with self-reported ethnicity.docx

BackgroundThe epidemiology of Mycobacterium tuberculosis complex (MTBC) lineage 5 (L5) infections in Ghana revealed a significantly increased prevalence in Ewes compared to other self-reported ethnic groups. In that context, we sought to investigate the early phase of tuberculosis (TB) infection using ex vivo infection of macrophages derived from the blood of Ewe and Akan ethnic group volunteers with MTBC L4 and L5 strains.MethodsThe study participants consisted of 16 controls, among which self-reported Akan and Ewe ethnicity was equally represented, as well as 20 cured TB cases consisting of 11 Akans and 9 Ewes. Peripheral blood mononuclear cells were isolated from both healthy controls and cured TB cases. CD14+ monocytes were isolated and differentiated into monocyte-derived macrophages (MDMs) before infection with L4 or L5 endemic strains. The bacterial load was assessed after 2 hours (uptake) as well as 3 and 7 days post-infection.ResultsWe observed a higher capacity of MDMs from Ewes to phagocytose L4 strains (p < 0.001), translating into a higher bacillary load on day 7 (p < 0.001) compared to L5, despite the higher replication rate of L5 in Ewe MDMs (fold change: 1.4 vs. 1.2, p = 0.03) among the controls. On the contrary, within macrophages from Akans, we observed a significantly higher phagocytic uptake of L5 (p < 0.001) compared to L4, also translating into a higher load on day 7 (p = 0.04). However, the replication rate of L4 in Akan MDMs was higher than that of L5 (fold change: L4 = 1.2, L4 = 1.1, p = 0.04). Although there was no significant difference in the uptake of L4 and L5 among cured TB cases, there was a higher bacterial load of both L4 (p = 0.02) and L5 (p = 0.02) on day 7 in Ewe MDMs.ConclusionOur results suggest that host ethnicity (driven by host genetic diversity), MTBC genetic diversity, and individual TB infection history are all acting together to modulate the outcome of macrophage infections by MTBC.

背景：在加纳，对结核分枝杆菌复合群（MTBC）谱系5（L5）感染流行病学的研究揭示了与其它自报族群相比，埃维族群的感染率显著升高。在此背景下，本研究旨在通过将源自埃维族和阿坎族志愿者血液的巨噬细胞与MTBC L4和L5菌株进行体外感染，来探究结核（TB）感染的早期阶段。方法：研究参与者包括16名对照组，其中阿坎族和埃维族自报族裔人数均等，以及20名治愈的TB病例，包括11名阿坎族和9名埃维族。从健康对照组和治愈的TB病例中分离外周血单核细胞。CD14+单核细胞被分离并分化为单核细胞来源的巨噬细胞（MDMs），随后用L4或L5地方性菌株进行感染。在感染后2小时（摄取）以及感染后3天和7天评估细菌载量。结果：我们观察到埃维族MDMs对L4菌株的吞噬能力较高（p < 0.001），相较于L5菌株，7天时的细菌载量也较高（p < 0.001），尽管在对照组中L5在埃维族MDMs中的复制率较高（倍数变化：1.4 vs. 1.2，p = 0.03）。相反，在阿坎族巨噬细胞中，我们观察到对L5菌株的吞噬摄取显著高于L4菌株（p < 0.001），7天时的细菌载量也较高（p = 0.04）。然而，L4在阿坎族MDMs中的复制率高于L5（倍数变化：L4 = 1.2，L5 = 1.1，p = 0.04）。尽管在治愈的TB病例中L4和L5的摄取没有显著差异，但在埃维族MDMs中，L4（p = 0.02）和L5（p = 0.02）的细菌载量在7天时均较高。结论：我们的结果表明，宿主族群（由宿主遗传多样性驱动）、MTBC遗传多样性和个体TB感染史共同调节了MTBC巨噬细胞感染的结局。