先天免疫记忆,先天细胞以更保护性的方式对继发性挑战做出反应的能力,是由暴露于传染性和其他外来和内源性物质引起的。工程纳米粒子是颗粒状的外源剂,因此,可以触发单核细胞和巨噬细胞的炎症反应,因此也可以诱导先天记忆。这里,我们已经评估了工程金纳米颗粒(AuNPs)诱导记忆反应或调节由微生物剂诱导的记忆反应的能力。使用的微生物制剂在可溶性与颗粒形式(MDP和革兰氏阳性细菌金黄色葡萄球菌;β-葡聚糖和产生β-葡聚糖的真菌白色念珠菌),以及被杀死的整个微生物(S.金黄色葡萄球菌,白色念珠菌)或活的(革兰氏阴性菌幽门螺杆菌)。在体外评估记忆反应,通过将来自2-7个个体供体的人原代单核细胞暴露于有或没有AuNP的微生物剂(初级反应),然后让他们休息6天,让他们回到基线,并最终用LPS(二级记忆反应)挑战它们。初级和记忆应答被测试为先天性/炎性细胞因子TNFα和其他炎性和抗炎因子的产生。虽然对可溶性微生物刺激诱导的反应无活性(胞壁酰二肽-MDP-,β-葡聚糖),AuNP部分降低了由完整微生物诱导的初级反应。AuNP也无法直接诱导记忆反应,但可以以有限的方式调节刺激诱导的记忆,限于一些试剂和一些细胞因子。因此,与AuNPs共同引发进一步加剧了MDP诱导的TNFα产生的耐受性,导致较少的炎症记忆反应。相反,幽门螺杆菌诱导的耐受仅相对于抗炎细胞因子IL-10下调,这将导致总体更多的炎性记忆反应.AuNP的这些作用可能取决于反应性颗粒表面与微生物组分和试剂之间的差异相互作用/缔合。这可能会导致曝光曲线的变化。作为一般观察,然而,供体与供体之间的记忆反应谱和对AuNPs的反应性差异很大,这表明先天记忆取决于个体的暴露史。
Innate immune memory, the ability of innate cells to react in a more protective way to secondary challenges, is induced by exposure to infectious and other exogeous and endogenous agents. Engineered nanoparticles are particulate exogenous agents that, as such, could trigger an inflammatory reaction in monocytes and macrophages and could therefore be also able to induce innate memory. Here, we have evaluated the capacity of engineered gold nanoparticles (AuNPs) to induce a memory response or to modulate the memory responses induced by microbial agents. Microbial agents used were in soluble vs. particulate form (MDP and the gram-positive bacteria Staphylococcus aureus; β-glucan and the β-glucan-producing fungi C. albicans), and as whole microrganisms that were either killed (S. aureus, C. albicans) or viable (the gram-negative bacteria Helicobacter pylori). The memory response was assessed in vitro, by exposing human primary monocytes from 2-7 individual donors to microbial agents with or without AuNPs (primary response), then resting them for 6 days to allow return to baseline, and eventually challenging them with LPS (secondary memory response). Primary and memory responses were tested as production of the innate/inflammatory cytokine TNFα and other inflammatory and anti-inflammatory factors. While inactive on the response induced by soluble microbial stimuli (muramyl dipeptide -MDP-, β-glucan), AuNPs partially reduced the primary response induced by whole microorganisms. AuNPs were also unable to directly induce a memory response but could modulate stimulus-induced memory in a circumscribed fashion, limited to some agents and some cytokines. Thus, the MDP-induced tolerance in terms of TNFα production was further exacerbated by co-priming with AuNPs, resulting in a less inflammatory memory response. Conversely, the H. pylori-induced tolerance was downregulated by AuNPs only relative to the anti-inflammatory cytokine IL-10, which would lead to an overall more inflammatory memory response. These effects of AuNPs may depend on a differential interaction/association between the reactive particle surfaces and the microbial components and agents, which may lead to a change in the exposure profiles. As a general observation, however, the donor-to-donor variability in memory response profiles and reactivity to AuNPs was substantial, suggesting that innate memory depends on the individual history of exposures.