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.

通过诱导先天记忆进行先天免疫调节是改变宿主先天免疫反应以减少或预防疾病的一种机制。微生物产品调节先天反应，具有即时和持久的效果。先天记忆的特点是增强（训练）或抑制（耐受）先天免疫反应，包括促炎细胞因子的产生，在引发事件后的二次暴露。为了研究 β-葡聚糖和卡介苗芽孢杆菌在猪细胞中诱导先天训练或耐受的能力，用引发激动剂（β-葡聚糖或卡介苗芽孢杆菌）培养猪单核细胞，然后在 5 天后用异源微生物激动剂以确定先天记忆的诱导。用来自酿酒酵母的 β-葡聚糖引发抑制 IL-1β 和 TNF-α 细胞因子对 LPS 再刺激的反应，表明处于耐受状态。然而，由于 LPS 再刺激增强了 IL-1β 和 TNF-α 基因表达和蛋白质产生，卡介苗芽孢杆菌引发在猪单核细胞中诱导了训练状态。我们提出了猪单核细胞先天记忆的第一个证据，即卡介苗（训练）或酿酒酵母β-葡聚糖（耐受性）。在体外诱导训练或耐受状态是识别激动剂以在动物水平上改变先天免疫系统以增强疾病抵抗力的第一步。