β-glucan Recognition Reprogramms Proline Catabolism and Innate Memory

 

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B704
Abstract ID: 5823

Presenting Author:
Jinendiran Sekar , Postdoctoral Fellow at Harbor-UCLA Med. Ctr., Lundquist Institute for Biomedical Innovation

Abstract:

Cells of the innate immune system undergo long-term epigenetic and metabolic changes in response to pathogen-associated molecular patterns. This mechanism occurs in responses to isolated fungal cell wall components such as β-glucan or in complex mixtures of heat-killed Candida albicans. Oral epithelial cells (OECs) provide a barrier against commensal fungi, and the first line of host defense against invading pathogens. These encounters result in β-glucan (BG) exposure and recognition of epithelial cells. Thus, we speculated if BG induces programmed memory in OECs. We established an in vitro model of epithelial BG programming, referred to as BG-programmed-OECs. We found that BG priming induces epigenetic remodeling via reduction in DNA methylation in human oral epithelial cells and modulated immune responses during C. albicans infection. Using metabolic approaches, we identified that β-glucan recognition induces proline catabolism via proline dehydrogenase (Prodh) to sustain the TCA cycle and mitochondrial oxidative functions. Proline catabolism was, in part, required for innate memory since inhibition of Prodh during BG stimulation decreased the expression of distinct cytokines during reinfection with C. albicans. Further, BGP-mice showed enhanced pro-inflammatory responses and fungal control in a mouse model of acute mucosal infection. In conclusion, our findings reveal that BG-induced proline catabolism is crucial for innate immune memory in oral epithelial cells.