|YANG, PENGXIN - Iowa State University
|TUGGLE, CHRISTOPHER - Iowa State University
Submitted to: International Veterinary Immunology Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 9/11/2023
Publication Date: N/A
Technical Abstract: Innate memory is associated with improved health outcomes and disease resilience in some human and animal trials. Trained immunity, a form of innate memory, occurs when exposure to a priming agent (e.g. bacillus Calmette-Guerin; BCG) induces epigenetic modifications in progenitor cells that results in heightened immune responses by innate immune cells (e.g. monocytes, NK cells) upon subsequent exposure to pathogen-associated molecular patterns. To determine if BCG induces trained immunity in young pigs, neonates (3-5 days of age, n=10/group) were administered BCG (BCG) or not inoculated (noBCG) and monocytes subsequently isolated for assessment of responses after ex vivo stimulation. Specifically, monocytes were cultured ex vivo for 4h (bulk RNAseqencing; gene expression) or 24h (ELISA; cytokine production) with either media alone, lipopolysaccharide (LPS; TLR4 agonist), or a synthetic triacylated lipopeptide (Pam3CSK4; TLR2/TLR1 agonist). Monocyte production of TNF was elevated in monocytes from BCG group compared to noBCG group after ex vivo culture with LPS, and a slight but not significant increase was observed following ex vivo Pam3CSK4 stimulation. On average, over 1,200 genes were differentially expressed in stimulated monocytes from BCG pigs compared to noBCG pigs, again suggesting BCG induction of trained immunity. More genes tended to be upregulated in LPS-stimulated monocytes collected 3wks after BCG inoculation when compared to 6wks after administration. Gene ontology (GO) analysis revealed cell to cell signaling, RNA processing, and metabolic process as primary enriched pathways. Monocyte nuclei collected 6wk after BCG inoculation were subjected to Assay for Transposase-Accessible Chromatin using sequencing (ATACseq) to assess changes in chromatin accessibility, an indication of epigenetic changes induced by BCG. Together these data present evidence of trained immunity in monocytes of neonatal pigs following BCG exposure and may represent a potential pathway for enhanced nonspecific disease resilience.