Pluto Bioinformatics

GSE134647: Targeting of IL-1 activity to CD8+ T cells mounts a strong antigen-specific cellular immune response and protects against influenza virus infection in mice

Bulk RNA sequencing

Abstract: Annual administration and reformulation of influenza vaccines is required for protection against seasonal infections. However, the induction of strong and long-lasting T cells is critical to reach broad and potentially lifelong antiviral immunity. The NLRP3 inflammasome and its product interleukin-1b (IL-1b) are pivotal mediators of cellular immune responses to influenza, yet, overactivation of these systems leads to side effects, which hamper clinical applications. Here, we present a bypass around these toxicities by targeting the activity of IL-1b directly to CD8+ T cells. Using this approach, we demonstrate safe inclusion of IL-1b as an adjuvant in vaccination strategies, leading to full protection of mice against a high influenza virus challenge dose by raising potent memory T cell responses. In conclusion, this paper proposes a new class of vaccine adjuvants and provides further insight in the mechanics of IL-1b-driven antiviral T cell immunity.; RNA-sequencing summary: To obtain insight in the transcriptome changes associated with the adjuvant properties of WT IL-1b and CD8a ALN-1, we performed RNA sequencing on CD8+ T cells sorted from lung parenchyma and lung-draining mediastinal LNs of vaccinated mice (WIV alone, WIV and WT IL-1, WIV and CD8 ALN-1) one week post-pH1N1 challenge. Altogether, these transcriptomics data indicate that WT IL-1b and CD8a ALN-1 provoke changes in the transcriptome of CD8+ T cells that are in line with the generation of potent and active CTLs with a memory phenotype, both in lung parenchyma and draining LNs. SOURCE: Bram Van Den Eeckhout (bram.vandeneeckhout@vib-ugent.be) - VIB-UGent