Impact of innate immune training on lung tissue resident memory formation following RSV infection 2328124

Abstract

Abstract Introduction Trained immunity is a well-documented phenomenon which can mediate non-specific immunity against pathogens. Secondary challenge following training results in increased production of proinflammatory mediators by innate immune cells. It has been previously shown that this inflammatory microenvironment can influence T cell responses and may alter the Th1/Th2 and Treg/Th17 balance. Here we examined the impact of trained immunity on lung tissue resident memory (Trm) formation and function following respiratory syncytial virus (RSV) infection. Methods Mice were treated intraperitoneally (i.p.) with compounds known to induce trained immunity seven days prior to intranasal infection with RSV. Disease severity was measured via weight loss and airway obstruction throughout initial training and subsequent RSV infection. Lungs and bronchoalveolar lavage (BAL) fluid were harvested 30 days post-RSV infection. Cells from the lung and BAL were stimulated ex vivo with RSV peptides to determine Trm cytokine production. Cells were then characterized using spectral flow cytometric analysis. Results Mice administered β-glucan i.p. prior to RSV infection exhibited a significant decrease in total CD8 Trm number and function in the airways at 30 days post-infection compared to RSV infection alone. RSV disease severity was not impacted by prior β-glucan treatment. Conclusion β-glucan is a well characterized trained immunity stimulus and is a promising adjuvant in vaccine development, with several ongoing clinical trials for both cancer and viral studies. However, our results suggest that β-glucan induced training decreases Trm numbers and function following RSV infection, highlighting the need for further studies in this area. Funding Source N/A Topic Categories Viral Immunology (VIR)