Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.
Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review.
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结核病和癌症中的乳酸代谢和信号转导：对比研究综述。
DOI：
10.3389/fcimb.2021.624607
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发表时间：
2021
影响因子：
5.7
通讯作者：
Basaraba RJ
中科院分区：
文献类型：
--
作者：
Kiran D;Basaraba RJ
感染结核分枝杆菌（Mtb）导致结核病（TB）疾病仍然是一个主要的全球卫生挑战。关键的障碍，包括但不限于多药耐药性的发展、缺乏检测潜伏性结核病患者的诊断方法、缺乏预防结核杆菌感染的有效疫苗以及使活动性结核病复杂化的传染性和非传染性合并症，继续阻碍结核病治愈的进展。为了补充正在进行的新型抗菌药物的开发，该领域的研究人员正在探索宿主导向疗法（HDTs）的价值。这种治疗策略针对宿主，而不是Mtb，旨在增强宿主对感染的反应，从而使宿主更好地预防或清除感染并解决慢性炎症。免疫细胞的代谢途径已被确定为有希望的HDT靶点，因为更多的代谢物和代谢途径已被证明在结核病的发病和疾病进展中发挥作用。具体来说，这篇综述强调了乳酸盐作为免疫调节代谢物和宿主对结核分枝杆菌感染反应中潜在的重要信号分子的潜在作用。虽然长期以来被认为是葡萄糖代谢的惰性最终产物，但癌症研究领域已经发现了乳酸在癌变和对化疗药物治疗的耐药性中的重要性。在此，我们讨论了在乳酸代谢背景下结核肉芽肿和肿瘤微环境之间的相似性，并确定了已被证明在肿瘤进展中发挥作用但尚未在结核背景下探索的关键代谢和信号通路。最终，乳酸代谢和信号可能成为结核病可行的HDT靶点；然而，在采用这种HDT策略之前，需要进行关键的额外研究，以更好地了解结核分枝杆菌感染期间乳酸盐在宿主-病原体界面的作用。
Infection with Mycobacterium tuberculosis (Mtb) leading to tuberculosis (TB) disease continues to be a major global health challenge. Critical barriers, including but not limited to the development of multi-drug resistance, lack of diagnostic assays that detect patients with latent TB, an effective vaccine that prevents Mtb infection, and infectious and non-infectious comorbidities that complicate active TB, continue to hinder progress toward a TB cure. To complement the ongoing development of new antimicrobial drugs, investigators in the field are exploring the value of host-directed therapies (HDTs). This therapeutic strategy targets the host, rather than Mtb, and is intended to augment host responses to infection such that the host is better equipped to prevent or clear infection and resolve chronic inflammation. Metabolic pathways of immune cells have been identified as promising HDT targets as more metabolites and metabolic pathways have shown to play a role in TB pathogenesis and disease progression. Specifically, this review highlights the potential role of lactate as both an immunomodulatory metabolite and a potentially important signaling molecule during the host response to Mtb infection. While long thought to be an inert end product of primarily glucose metabolism, the cancer research field has discovered the importance of lactate in carcinogenesis and resistance to chemotherapeutic drug treatment. Herein, we discuss similarities between the TB granuloma and tumor microenvironments in the context of lactate metabolism and identify key metabolic and signaling pathways that have been shown to play a role in tumor progression but have yet to be explored within the context of TB. Ultimately, lactate metabolism and signaling could be viable HDT targets for TB; however, critical additional research is needed to better understand the role of lactate at the host-pathogen interface during Mtb infection before adopting this HDT strategy.