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Plants are capable of mounting an immune defense in response to infection, wounding, or environmental stress. The immune response of a plant is often mediated through the recognition of conserved molecular motifs associated with stress. Treating plants with these molecular motifs prior to exposure to stress, termed immune priming, can improve plant resilience to subsequent stressors. Here, we demonstrate the use of cellulose nanocrystals (CNCs) as an immune priming tool for Arabidopsis thaliana combining phenotypic and transcriptomic data to validate the efficacy of CNCs as an immune primer. Pretreatment of Arabidopsis with CNCs reduces the level of infection by the pathogen Pseudomonas syringae up to 65%. RNA sequencing shows that treatment of Arabidopsis with CNCs results in deep transcriptional reprogramming, perturbing over 1300 genes, most of which are associated with immune regulation. We hypothesize plants recognize CNCs as cell-wall damage, potentially explaining the observed immune response. Finally, physiological characterization of the plant response to CNCs demonstrates minimal effects on plant growth without inducing callose deposition or generation of reactive oxygen species. This work provides a foundation for future investigation of cellulose-based nanomaterials as immune primers, particularly in crop species. Given their ease of synthesis, low cost, degradability, and bio/environmental compatibility, cellulose-based materials could serve as a complement to conventional biocides for pathogen control.