Differential induction of innate memory in porcine monocytes by β-glucan or bacillus Calmette-Guerin

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 pro-inflammatory cytokine production, to secondary exposure following a priming event. To investigate the ability of β-glucans and bacillus Calmette-Guerin to induce innate training or tolerance in pig cells, porcine monocytes were cultured with priming agonist (β-glucans or bacillus Calmette-Guerin) then re-stimulated 5 d later with a heterologous microbial agonist to determine induction of innate memory. Priming with β-glucan from Saccharomyces cerevisiae depressed IL-1β and TNF-α cytokine responses to re-stimulation with LPS, indicative of a tolerized state. However, bacillus Calmette-Guerin priming induced a trained state in porcine monocytes, as LPS re-stimulation enhanced IL-1β and TNF-α gene expression and protein production. We present the first evidence of innate memory in pig monocytes, with bacillus Calmette-Guerin (training) or Saccharomyces cerevisiae β-glucan (tolerance). Induction of a trained or tolerized state in vitro is a first step to identify agonists to alter the innate immune system at the animal level with the intent of enhancing disease resistance.

Reference Transcriptomes of Porcine Peripheral Immune Cells Created Through Bulk and Single-Cell RNA Sequencing

“…All animal procedures were performed in compliance with and approval by NADC Animal Care and Use Committee. PBMCs were isolated, enumerated, and viability assessed as previously described ( Byrne et al, 2020 ).…”

The innate immune stimulant Amplimune® is safe to administer to young feedlot cattle

“…In this trained state, the innate immune system has a heightened ability to deal with a wide range of pathogens that the host may encounter 19 . Armed with this new knowledge, researchers have been investigating the potential for innate immune stimulants, including Mycobacterium bovis and β‐glucan from Saccharomyces cerevisiae , to be used to provide short‐term protection against a broad range of diseases 20,21 . Indeed, trained immunity has been shown to be effective in stimulating the immune system to help prevent and treat a variety of diseases in farm animals 21–23 …”

“…19 Armed with this new knowledge, researchers have been investigating the potential for innate immune stimulants, including Mycobacterium bovis and β-glucan from Saccharomyces cerevisiae, to be used to provide short-term protection against a broad range of diseases. 20,21 Indeed, trained immunity has been shown to be effective in stimulating the immune system to help prevent and treat a variety of diseases in farm animals. [21][22][23] Amplimune® is a commercially available innate immune stimulant, based on mycobacterium cell wall fractions (MCWF) of Mycobacterium phlei, a non-pathogenic mycobacterium found in abundance in the natural environment.…”

Heat inactivated mycobacteria, alpha‐Gal and zebrafish: Insights gained from experiences with two promising trained immunity inductors and a validated animal model

“…This reduction in infant mortality is mainly associated to BCG-induced cross-protection against unrelated pathogens, especially sepsis and respiratory infections [60,61]. Furthermore, BCG also provided the first experimental evidence of TRAIM [62], and has become one of the most studied TRAIM inducers [18,53,[63][64][65][66][67][68][69][70][71]. Over the last decades, several experimental studies have reported that BCG stimulation induces protection upon a secondary encounter with unrelated pathogens such as herpes simplex virus [72,73], influenza virus [72,74,75], Staphilococcus aureus (S. aureus) [64,76], Salmonella enteritidis [62], Leishmania major [77], Plasmodium spp.…”