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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Food Safety and Enteric Pathogens Research » Research » Publications at this Location » Publication #400891

Research Project: Intestinal Microbial Ecology and Non-Antibiotic Strategies to Limit Shiga Toxin-Producing Escherichia coli (STEC) and Antimicrobial Resistance Transmission in Food Animals

Location: Food Safety and Enteric Pathogens Research

Title: Intravenous BCG induction of innate memory in young pigs

item Byrne, Kristen
item Loving, Crystal

Submitted to: American Association of Immunologists Proceedings
Publication Type: Abstract Only
Publication Acceptance Date: 2/24/2022
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Exposure to vaccine strain of Mycobacterium bovis (M. bovis), Bacillus Calmette-Guerin (BCG), alters innate immune cells through epigenetic and metabolic modifications resulting in heightened responses to subsequent microbial insult (innate memory). As a biomedical model for human disease, pigs provide a critical space to study the role of innate memory in disease resistance. Young pigs were inoculated intravenous (IV) or intraperitoneal (IP) with either live or heat-inactivated BCG (IV-live, IP-live, IV-inactive, noBCG groups). At 2wks post BCG inoculation, monocyte production of IL-1ß nor TNF cytokines following ex vivo stimulation with LPS was not different in any BCG group compared to noBCG, i.e. no innate memory. As dose of live BCG was lower than anticipated, at 3wks post primary inoculation, all pigs were inoculated a second time with respective preparations and routes of BCG. Ex vivo cytokine production in LPS stimulated monocytes was measured again at 5wks post primary inoculation (2wks post-secondary inoculation) and both IL-1ß and TNF cytokines were elevated in IV-live (innate memory), but not IP-live or IV-inactive groups. Additionally, ex vivo stimulation of PBMC with homologous recall antigen (purified proteins from M. bovis) resulted in a 3-fold higher IFN' response in IP-live compared to IV-live and no IFN' production in noBCG or IV-inactive. Together these data suggest that while BCG can induce a state of innate memory in monocytes of young pigs, induction of training cannot be inferred by T cell production of IFN' to recall protein antigen. Additionally, data continue to highlight pigs as a valuable model as multiple BCG factors (i.e. route, dose, or viability) may need to be considered for induction of innate memory.