Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection

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.