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Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection. 2021
Mauro Di Pilato, and
Miguel Palomino-Segura, and
Ernesto Mejías-Pérez, and
Carmen E Gómez, and
Andrea Rubio-Ponce, and
Rocco D'Antuono, and
Diego Ulisse Pizzagalli, and
Patricia Pérez, and
Raphael Kfuri-Rubens, and
Alberto Benguría, and
Ana Dopazo, and
Iván Ballesteros, and
Carlos Oscar S Sorzano, and
Andrés Hidalgo, and
Mariano Esteban, and
Santiago F Gonzalez
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland. mdi@mdanderson.org.
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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