Di Pilato Mauro, Palomino-Segura Miguel, Mejías-Pérez Ernesto, Gómez Carmen E, Rubio-Ponce Andrea, D'Antuono Rocco, Pizzagalli Diego Ulisse, Pérez Patricia, Kfuri-Rubens Raphael, Benguría Alberto, Dopazo Ana, Ballesteros Iván, Sorzano Carlos Oscar S, Hidalgo Andrés, Esteban Mariano, Gonzalez Santiago F
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología-CSIC, Madrid, Spain.
NPJ Vaccines. 2021 Apr 12;6(1):52. doi: 10.1038/s41541-021-00314-7.
Neutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.
中性粒细胞是参与病原体清除的固有免疫细胞，也可诱导适应性免疫反应。已有研究描述了Nα和Nβ中性粒细胞在体外产生抗原特异性CD8 T细胞反应的能力不同。然而，这些细胞类型在体内如何发挥作用，以及Nβ/Nα比值的操纵如何影响疫苗介导的免疫反应尚不清楚。在本研究中，我们发现这些中性粒细胞亚型在痘苗病毒（VACV）感染后在脾脏中表现出不同的迁移和运动模式以及与CD8 T细胞相互作用的不同能力。此外，在分析粘附、炎症和迁移标志物后，我们观察到与Nα相比，Nβ中性粒细胞α4β1整合素过度表达。最后，通过抑制α4β1整合素，我们提高了Nβ/Nα比值，并增强了CD8 T细胞对HIV VACV递送抗原的反应。这些发现为理解基于中性粒细胞对适应性免疫系统的控制及其在疫苗设计中的相关性提供了重大进展。
