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

Abstract

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.

Neutrophils in pregnancy: New insights into innate and adaptive immune regulation

“…This hybrid population expresses markers of both neutrophils (Ly6G) and DCs (CD11c, MHC‐II, CD80 and CD86) and exhibits properties reserved for these individual cell types such as probing motion, antigen presentation and extrusion of neutrophil extracellular traps and bactericidal properties via cathelicidin production [ 76 , 77 ]. Importantly, neutrophils not only function as APCs for CD4 + T cells but also present antigen to CD8 + T cells [ 45 , 78 ]. The role of neutrophil‐derived cathelicidin in regulating T‐cell responses is further demonstrated in a recent paper by Minns et al [ 72 ].…”

“…Further investigation into the role of neutrophil granule contents in controlling T‐cell responses in pregnancy is warranted. Another mechanism utilized by neutrophils to promote T‐cell activation is the release of neutrophil extracellular traps (NETs) [ 45 , 78 ]. NETting neutrophils were in fact shown to promote priming of CD4 + T cells, increasing their expression of CD25 and CD69 and lowering their activation threshold.…”

Solubilized curcuminoid complex prevents extensive immunosuppression through immune restoration and antioxidant activity: Therapeutic potential against SARS-CoV-2 (COVID-19)

“…Neutrophils, which are important innate cells involved in the clearance of acute bacterial and viral infections, may help activate APCs, NK cells, and T cells [32] , [33] . To evaluate whether neutrophil activation is increased or decreased by C—S/M treatment, we next assessed neutrophil activation in CTX-injected mice following pre-treatment with C—S/M.…”

Neutrophil Functional Heterogeneity and Implications for Viral Infections and Treatments

“…They were named Nα and Nβ, with Nβ being larger, more lobulated, and more segmented than Nα. Both of these neutrophil populations have been described to have an in vitro capacity to generate antigen-specific CD8 + T cell responses after recruitment by cytokines associated with the pro-inflammatory environment following infection [138]. However, Nβ were observed to be more mobile and showed a greater capacity to act as an APC to activate virus-specific CD8 T cells [138].…”

“…Both of these neutrophil populations have been described to have an in vitro capacity to generate antigen-specific CD8 + T cell responses after recruitment by cytokines associated with the pro-inflammatory environment following infection [138]. However, Nβ were observed to be more mobile and showed a greater capacity to act as an APC to activate virus-specific CD8 T cells [138]. They also expressed higher concentrations of the epitope-expressing molecule MHC class II and co-stimulatory molecules CD11, CD80, and CD86 than Nα, further supporting their enhanced ability to act as APCs compared to Nα [137,138].…”