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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 #406920
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: BCG induced innate training in neonatal and weaned pigs is dependent on route of administration

Author
item Loving, Crystal
item Byrne, Kristen

Submitted to: International Veterinary Immunology Symposium
Publication Type: Abstract Only
Publication Acceptance Date: 9/11/2023
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: A potential immunomodulation mechanism for improving disease resilience is innate training, which relies on epigenetic modifications of immune cells for a heightened (ie, trained) response upon repeated microbial stimulation. Prior experiences indicate bacillus Calmette-Guerin (BCG) exposure increases cytokine production upon secondary exposure to microbe-associated molecular patterns, and epidemiological data suggest improved disease resistance in humans administered neonatal BCG. A series of studies were performed in neonatal (2-5 days) and weaned (18-22 days) pigs in which BCG was administered by the subcutaneous (SQ), intramuscular (IM), intraperitoneal (IP), or intravenous (IV) route to assess induction of innate training. Monocytes isolated from pigs approximately 2-3 weeks and/or 5-6 weeks after BCG administration were stimulated with LPS or media alone. Supernatants were collected for assessment of TNF and IL1B production. Only following IV administration was innate training consistently detected, noted by increased production of TNF or IL1B following LPS stimulation of monocytes from BCG group. No other route of administration induced innate training. Peripheral blood mononuclear cells (PBMC) were also collected at indicated time points following BCG administration for assessment of classic T cell recall response to purified protein derivative (PPD) antigens. Specifically, PBMC were stimulated with PPD and IFNg in supernatants measured. Interestingly, an inverse relationship between adaptive immune response to PPD antigen and innate training was often noted. Following IM or SQ inoculation, IFNg production by PBMC from BCG group was detected, but innate training was not. Following IV inoculation, IFNg production by PBMC from BCG group was not significantly increased over mock group, but innate training was detected. BCG was recovered from peripheral tissues at necropsy, including the bone marrow. Overall, BCG administration resulted in enhanced cytokine production ex vivo by monocytes after LPS exposure in both neonatal and weaned age pigs, but only when administered IV.