Tuberculosis kills more than 1 million people every year, and its control depends on the effective mechanisms of innate immunity, with or without induction of adaptive immune response. We investigated the interaction of type II alveolar epithelial cells (AEC‐II) infected by Mycobacterium tuberculosis with dendritic cells (DCs). We hypothesized that the microenvironment generated by this interaction is critical for the early innate response against mycobacteria. We found that AEC‐II infected by M. tuberculosis induced DC maturation, which was negatively regulated by HIF‐1α‐inducible NOS2 axis, and switched DC metabolism from an early and short peak of glycolysis to a low energetic status. However, the infection of DCs by M. tuberculosis up‐regulated NOS2 expression and inhibited AEC‐II‐induced DC maturation. Our study demonstrated, for the first time, that HIF‐1α‐NOS2 axis plays a negative role in the maturation of DCs during M. tuberculosis infection. Such modulation might be useful for the exploitation of molecular targets to develop new therapeutic strategies against tuberculosis.

中文翻译：

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结核分枝杆菌感染的肺泡上皮细胞通过HIF-1α-NOS2轴调节树突状细胞的功能。

结核病每年杀死超过100万人，其控制取决于先天免疫的有效机制，无论是否诱发适应性免疫应答。我们研究了结核分枝杆菌感染的II型肺泡上皮细胞（AEC-II）与树突状细胞（DC）的相互作用。我们假设这种相互作用产生的微环境对于针对分枝杆菌的早期先天反应至关重要。我们发现被结核分枝杆菌感染的AEC-II诱导了DC成熟，DC成熟受到HIF-1α诱导的NOS2轴的负调控，并且将DC代谢从糖酵解的早期和短峰切换为低能量状态。然而，结核分枝杆菌感染DC上调NOS2表达并抑制AEC-II诱导的DC成熟。我们的研究首次证明，HIF-1α-NOS2轴在结核分枝杆菌感染过程中对DC的成熟起负面作用。这种调节对于利用分子靶标开发新的抗结核治疗策略可能有用。