Journal
NPJ VACCINES
Volume 6, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41541-021-00314-7
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Funding
- FEBS Short-Term Fellowship
- Marie Curie Global Fellowship [750973]
- FEBS Long-Term Fellowship
- Swiss National Foundation (SNF) grants, R'equipt [145038]
- Ambizione [148183]
- European Commission Marie Curie Reintegration Grant [612742]
- Formacion del Profesorado Universitario
- EMBO Short-Term Fellowship
- SystemsX.ch [2013/124]
- Ministerio de Ciencia e Innovacion Fellowships [BES-2016-076635, RTI2018- 095497-B-I00]
- AIDS Research Network [RD16/0025/0014-ISCIII-FEDER]
- PTVDC Program
- Bill & Melinda Gates Foundation
- [SAF-2017-88089-R-Mineco-FEDER]
- Marie Curie Actions (MSCA) [750973] Funding Source: Marie Curie Actions (MSCA)
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This study reveals that N beta and N alpha neutrophils exhibit different migratory patterns and interactions with CD8 T cells in vivo following VACV infection. N beta neutrophils overexpress the alpha 4 beta 1 integrin compared to N alpha. Inhibiting alpha 4 beta 1 integrin can increase the N beta/N alpha ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens.
Neutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. N alpha and N beta 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 N beta/N alpha 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 N beta neutrophils overexpress the alpha 4 beta 1 integrin compared to N alpha. Finally, by inhibiting alpha 4 beta 1 integrin, we increase the N beta/N alpha 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.
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