Ardali Razieh, Garcia-Nicolas Obdulio, Ollagnier Catherine, Sánchez Carvajal José María, Levy Maria, Yvernault Pauline, de Aboim Borges Fialho de Brito Francisco, Summerfield Artur
Institute of Virology and Immunology, 3147 Mittelhäusern, Switzerland.
Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Vaccines (Basel). 2024 Aug 29;12(9):982. doi: 10.3390/vaccines12090982.
The non-specific protective effects offered by the concept of "innate immune memory" might represent a promising strategy to tackle early-life threatening infections. Here we tested the potential of an in vitro selected β-glucan in inducing trained immunity using an in vivo porcine model. We assessed the leukocyte transcriptome using blood transcriptomic module (BTM), proinflammatory cytokines, and clinical scoring after a first "training" and a second "stimulation" phase. The possible induction of innate immune memory was tested during a "stimulation" by an LPS-adjuvanted vaccine (Hyogen) one day after weaning. Following the "training", no major group differences were found, with the exception of a plasma TNF that was only induced by Adj and Adj_BG treatment. After vaccination, all groups developed similar antibody responses. A significant induction of plasma TNF and IL-1β was found in groups that received Adj and Adj_BG. However, following vaccination, the expected early innate BTMs were only induced by the PBS group. In conclusion, the adjuvant alone, adjuvant-formulated β-glucan, or orally applied β-glucan were unable to enhance innate immune reactivity but rather appeared to promote innate immune tolerance. Such an immune status could have both positive and negative implications during this phase of the piglet's life.
“固有免疫记忆”概念所提供的非特异性保护作用可能是应对危及生命早期感染的一种有前景的策略。在此,我们使用体内猪模型测试了体外筛选的β-葡聚糖诱导训练免疫的潜力。我们在第一个“训练”阶段和第二个“刺激”阶段后,使用血液转录组模块(BTM)、促炎细胞因子和临床评分评估白细胞转录组。在断奶后一天,通过脂多糖佐剂疫苗(Hyogen)进行“刺激”期间,测试了固有免疫记忆的可能诱导情况。“训练”后,除了仅由佐剂和佐剂-β-葡聚糖处理诱导的血浆肿瘤坏死因子(TNF)外,未发现主要组间差异。接种疫苗后,所有组产生了相似的抗体反应。在接受佐剂和佐剂-β-葡聚糖的组中发现血浆TNF和白细胞介素-1β(IL-1β)有显著诱导。然而,接种疫苗后,预期的早期固有BTM仅由磷酸盐缓冲盐水(PBS)组诱导。总之,单独的佐剂、佐剂配制的β-葡聚糖或口服的β-葡聚糖均无法增强固有免疫反应性,反而似乎促进了固有免疫耐受。这种免疫状态在仔猪生命的这个阶段可能具有积极和消极的影响。