Innate Immunomodulation in Food Animals: Evidence for Trained Immunity?

Abstract

Antimicrobial resistance (AMR) is a significant problem in health care, animal health, and food safety. To limit AMR, there is a need for alternatives to antibiotics to enhance disease resistance and support judicious antibiotic usage in animals and humans. Immunomodulation is a promising strategy to enhance disease resistance without antibiotics in food animals. One rapidly evolving field of immunomodulation is innate memory in which innate immune cells undergo epigenetic changes of chromatin remodeling and metabolic reprogramming upon a priming event that results in either enhanced or suppressed responsiveness to secondary stimuli (training or tolerance, respectively). Exposure to live agents such as bacille Calmette-Guerin (BCG) or microbe-derived products such as LPS or yeast cell wall ß-glucans can reprogram or "train" the innate immune system. Over the last decade, significant advancements increased our understanding of innate training in humans and rodent models, and strategies are being developed to specifically target or regulate innate memory. In veterinary species, the concept of enhancing the innate immune system is not new; however, there are few available studies which have purposefully investigated innate training as it has been defined in human literature. The development of targeted approaches to engage innate training in food animals, with the practical goal of enhancing the capacity to limit disease without the use of antibiotics, is an area which deserves attention. In this review, we provide an overview of innate immunomodulation and memory, and the mechanisms which regulate this long-term functional reprogramming in other animals (e.g., humans, rodents). We focus on studies describing innate training, or similar phenomenon (often referred to as heterologous or non-specific protection), in cattle, sheep, goats, swine, poultry, and fish species; and discuss the potential benefits and shortcomings of engaging innate training for enhancing disease resistance.

Glucose Oligosaccharide and Long-Chain Glucomannan Feed Additives Induce Enhanced Activation of Intraepithelial NK Cells and Relative Abundance of Commensal Lactic Acid Bacteria in Broiler Chickens

“…The enhanced activation of intraepithelial NK cells was observed after the first seven days of supplementation and subsequently decreased to levels similar to those observed in the control group. NK cells were shown to be involved in trained immunity in livestock [71] and humans [72]. Initial exposure to β-glucans and BCG vaccination induced responses of monocytes and NK cells, respectively, thereby priming these innate cells, and a subsequent exposure to bacterial components led to increased innate responses, conferring innate memory.…”

Piscine Orthoreovirus (PRV)-3, but Not PRV-2, Cross-Protects against PRV-1 and Heart and Skeletal Muscle Inflammation in Atlantic Salmon

“…Modern farming of Atlantic salmon ( Salmo salar ) is characterized by high-density populations, rapid growth, short production cycles, and artificial adaptation to sea water. This life cycle does not ensure natural pathogen exposure in early life or the natural training of the fish innate immune system [ 1 ]. When transferred to the sea, the untrained immune system may not be ready to handle the novel repertoire of pathogens.…”

Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models

“…Further, BCG-vaccinated piglets had a higher number of activated monocytes at 4 and 6 weeks of life compared to unvaccinated piglets, and this trend continued as the piglets aged and after they received the Mtb challenge (Ramos et al, 2019). This active monocyte population could have been undergoing epigenetic reprogramming and trained immunity, a process that BCG induces in humans (Byrne et al, 2020). However, affirming this will require further study (Marinova et al, 2017).…”