Division of Infectious Diseases & International Health, Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
Department of Enteric Diseases, Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand.
Semin Cell Dev Biol. 2019 Apr;88:119-128. doi: 10.1016/j.semcdb.2018.02.003. Epub 2018 Feb 21.
Chemokines are a family of small proteins best known for their ability to orchestrate immune cell trafficking and recruitment to sites of infection. Their role in promoting host defense is multiplied by a number of additional receptor-dependent biological activities, and most, but not all, chemokines have been found to mediate direct antimicrobial effects against a broad range of microorganisms. The molecular mechanism(s) by which antimicrobial chemokines kill bacteria remains unknown; however, recent observations have expanded our fundamental understanding of chemokine-mediated bactericidal activity to reveal increasingly diverse and complex actions. In the current review, we present and consider mechanistic insights of chemokine-mediated antimicrobial activity against bacteria. We also discuss how contemporary advances are reshaping traditional paradigms and opening up new and innovative avenues of research with translational implications. Towards this end, we highlight a developing framework for leveraging chemokine-mediated bactericidal and immunomodulatory effects to advance pioneering therapeutic approaches for treating bacterial infections, including those caused by multidrug-resistant pathogens.
趋化因子是一小类蛋白质家族,其功能是协调免疫细胞向感染部位的迁移和募集,这一功能最为人所知。趋化因子在促进宿主防御方面的作用,还可以通过多种其他受体依赖性的生物学活性来增强,而且大多数(但不是全部)趋化因子已被发现具有针对广泛微生物的直接抗菌作用。具有抗菌作用的趋化因子杀死细菌的分子机制尚不清楚;然而,最近的观察结果扩展了我们对趋化因子介导的杀菌活性的基本理解,揭示了越来越多样化和复杂的作用。在当前的综述中,我们提出并考虑了趋化因子介导的抗细菌活性的机制见解。我们还讨论了当前的进展如何重塑传统的范例,并为具有转化意义的研究开辟新的和创新的途径。为此,我们强调了一个不断发展的框架,用于利用趋化因子介导的杀菌和免疫调节作用,推进治疗细菌感染的开创性治疗方法,包括多药耐药病原体引起的感染。