TY - JOUR
T1 - Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection
AU - Di Pilato, Mauro
AU - Palomino-Segura, Miguel
AU - Mejías-Pérez, Ernesto
AU - Gómez, Carmen E.
AU - Rubio-Ponce, Andrea
AU - D’Antuono, Rocco
AU - Pizzagalli, Diego Ulisse
AU - Pérez, Patricia
AU - Kfuri-Rubens, Raphael
AU - Benguría, Alberto
AU - Dopazo, Ana
AU - Ballesteros, Iván
AU - Sorzano, Carlos Oscar S.
AU - Hidalgo, Andrés
AU - Esteban, Mariano
AU - Gonzalez, Santiago F.
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41541-021-00314-7
DO - 10.1038/s41541-021-00314-7
M3 - Article
C2 - 33846352
AN - SCOPUS:85104232165
SN - 2059-0105
VL - 6
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 52
ER -