Identification of IL-27 producers in a neonatal BCG vaccination model.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B919
Abstract ID: 4631

Presenting Author:
Ashley M Divens , PhD Candidate at West Virginia Univ. Sch. of Med.

Abstract:

The live-attenuated BCG vaccine fails to confer long-lasting protection against tuberculosis (TB), allowing TB to remain a global health concern. BCG is administered during the neonatal period, when the immunosuppressive cytokine IL-27 is elevated. We have shown that BCG vaccination further increases these levels. Studies show the specific cellular source of IL-27 can influence T cell responses, but the source following BCG vaccination is unknown. We hypothesized that specific populations of myeloid cells with immune suppressive activity are the dominant IL-27 producers following BCG vaccination. We used a novel neonatal BCG vaccination model to immunize 7-day old IL-27p28eGFP reporter mice and developed a flow cytometry panel to identify myeloid cell populations. GFP expression, indicative of IL-27 production, was increased in both spleens and lungs at 5 weeks post-vaccination. The dominant population in both tissues was F4/80+ and a significant increase in MHCII expression along with IL-27 production following vaccination suggests improved antigen presentation. A MHCII+ subpopulation that also expresses CD11c and F4/80 was more abundant in the spleen, whereas a different MHCII+ subpopulation that expresses Ly6G/C and F4/80 expanded in the lung. Single-cell RNA sequencing data further supported the functionality of the IL-27 producers. Overall, the dominant producers of IL-27 following vaccination include unique populations of macrophages that are tissue-dependent.