Transmission phenotype of <i>Mycobacterium tuberculosis</i> strains is mechanistically linked to induction of distinct pulmonary pathology

In a study of household contacts (HHC), households were categorized into High (HT) and Low (LT) transmission groups based on the proportion of HHC with a positive tuberculin skin test. The Mycobacterium tuberculosis (Mtb) strains from HT and LT index cases of the households were designated Mtb-HT and Mtb-LT, respectively. We found that C3HeB/FeJ mice infected with Mtb-LT strains exhibited significantly higher bacterial burden compared to Mtb-HT strains and also developed diffused inflammatory lung pathology. In stark contrast, a significant number of mice infected with Mtb-HT strains developed caseating granulomas, a lesion type with high potential to cavitate. None of the Mtb-HT infected animals developed diffused inflammatory lung pathology. A link was observed between increased in vitro replication of Mtb-LT strains and their ability to induce significantly high lipid droplet formation in macrophages. These results support that distinct early interactions of Mtb-HT and Mtb-LT strains with macrophages and subsequent differential trajectories in pathological disease may be the mechanism underlying their transmission potential.在一项针对家庭接触者（household contacts, HHC）的研究中，研究人员依据结核菌素皮肤试验阳性的家庭接触者占比，将纳入研究的家庭划分为高传播组（HT）与低传播组（LT）。来自HT组与LT组家庭原发病例的结核分枝杆菌（Mycobacterium tuberculosis, Mtb）菌株，分别被命名为Mtb-HT与Mtb-LT。研究发现，感染Mtb-LT菌株的C3HeB/FeJ小鼠，其肺部细菌负荷显著高于感染Mtb-HT菌株的小鼠，同时还出现了弥漫性炎症性肺部病理表现。与之形成鲜明对比的是，感染Mtb-HT菌株的大量小鼠形成了干酪样肉芽肿——这是一种具有高空洞化潜能的病变类型，而感染Mtb-HT菌株的动物均未出现弥漫性炎症性肺部病理。研究还观察到，Mtb-LT菌株的体外增殖能力增强，与其诱导巨噬细胞产生大量脂滴的能力存在显著关联。上述结果表明，Mtb-HT与Mtb-LT菌株和巨噬细胞的早期相互作用存在差异，后续的病理疾病进程也各不相同，这可能是二者传播潜能存在差异的潜在机制。