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

Di Pilato, Mauro; Palomino-Segura, Miguel; Mejias-Perez, Ernesto; Gomez, Carmen E.; Rubio-Ponce, Andrea; D'Antuono, Rocco; Pizzagalli, Diego Ulisse; Perez, Patricia; Kfuri-Rubens, Raphael; Benguria, Alberto; Dopazo, Ana; Ballesteros, Ivan; Sorzano, Carlos Oscar S.; Hidalgo, Andres; Esteban, Mariano und Gonzalez, Santiago F. (2021): Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection. In: Npj Vaccines, Bd. 6, Nr. 1, 52

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch