Submitted to: Innate Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/25/2020
Publication Date: 8/30/2020
Citation: Byrne, K.A., Tuggle, C., Loving, C.L. 2020. Differential induction of innate memory in porcine monocytes by B-glucan or bacillus Calmette-Guerin. Innate Immunity. https://doi.org/10.1177/1753425920951607.
Interpretive Summary: All mammals have two types of immune systems (innate and adaptive) that recognize and attack viruses, bacteria, or yeast. The innate immune system was originally thought to respond to the same organism the same way every time; however, specific cells of the innate immune system in humans and mice can change their response to disease causing agents based on what they have “seen” in the recent past. By changing the responsiveness of innate immune cells, the animal is better able to respond and clear the virus, bacteria, or yeast. In pigs, innate immune cells pre-exposed to zymosan (component of yeast cell wall) had decreased innate inflammatory responses upon subsequent exposure to a bacterial cell wall component, lipopolysaccharide (LPS). However, innate immune cells pre-exposed to bacillus Calmette-Guerin (BCG), the tuberculosis vaccine, had increased inflammatory responses to restimulation with LPS. Our research shows that an important cell of the innate immune system can be altered for subsequent increased or decreased immune responses. The subsequent response was dependent on the initial foreign agent “seen” by the cell. This study represents a step toward modulating the innate immune system in pigs towards memory to better fight disease without the use of antibiotics.
Technical Abstract: Innate immunomodulation via induction of innate memory is one mechanism to alter the host’s innate immune response to reduce or prevent disease. Microbial products modulate innate responses with immediate and lasting effects. Innate memory is characterized by enhanced (training) or depressed (tolerance) innate immune responses, including proinflammatory cytokine production, to secondary exposure following a priming event. To investigate the ability of beta-glucans and bacillus Calmette-Guerin (BCG) to induce innate training or tolerance in pig cells, porcine monocytes were cultured with priming agonist (beta-glucans or BCG) and then restimulated 5 days later with a heterologous microbial agonist to determine induction of innate memory. Priming with beta-glucan from Saccharomyces cerevisiae depressed IL-1beta and TNF cytokine responses to restimulation with lipopolysaccharide (LPS), indicative of a tolerized state. However, BCG priming induced a trained state in porcine monocytes, as LPS restimulation enhanced IL-1beta and TNF gene expression and protein production. We present the first evidence of innate memory in pig monocytes, with BCG (training) or S. cerevisiae beta-glucan (tolerance). Induction of a trained or tolerized state in vitro is a first step to identifying agonists to alter the innate immune system at the animal level with the intent of enhancing disease resistance.