Abstract
This study explores the significance of antigenic nanoformulation in immunomodulation and in the interplay between immune response and nutrition. The work involves the development of a polylactic-co-glycolic acid (PLGA) biopolymer-based nanoparticle with immunogenic inclusions derived from Staphylococcus aureus cell wall and membrane (CWM) through a double emulsion method followed by their physio-chemical characterization and in vivo assessment in Caenorhabditis elegans (C. elegans). The prepared nanoparticles were monodispersed in nature and exhibited a diameter of ~ 25 nm with stable colloidal nature and a zeta potential of - 25 ± 2 mV. The inclusion release and carrier degradation profiling revealed controlled and steady kinetics supporting the sustained availability of the encapsulated payload. The immunomodulatory studies conducted in C. elegans revealed that the expression of the stress indicator gene viz., sodh-1 was significantly upregulated in the CWM-treated worms and was notably reduced in the worms treated with the nanoformulation indicative of the slow release of the antigen which does not trigger untoward stress responses. In contrast, the expression of host defense genes viz., clec-7, ilys-3, igg-1, and cyp-37B1 in response to the CWM treatment was found to be downregulated, while for the nanoformulation treatment, the extent of downregulation was relatively lesser. A notable observation emerged as these genes, previously downregulated, exhibited a significant upsurge when the nutritional supplementation was amplified. This highlighted the profound influence of nutrition in fine-tuning the immune responses. Our data offers insights that could pave the way for further research in designing nutritional strategies to augment immunomodulatory interventions, as well as advocate for nanoparticle-based immunomodulatory approaches to prevent immune stress.