Abstract
Innate immune memory is characterized by a modulation in the magnitude with which innate immune cells such as monocytes and macrophages respond to potential dangers, subsequent to previous exposure to the same or unrelated agents. In this study, we have examined the capacity of gold nanoparticles (AuNP), which are already in use for therapeutic and diagnostic purposes, to modulate the innate memory induced by bacterial agents. The induction of innate memory was achieved in vitro by exposing human primary monocytes to bacterial agents (lipopolysaccharide -LPS-, or live Bacille Calmette-Guérin -BCG) in the absence or presence of AuNP. After the primary activation, cells were allowed to return to a resting condition, and eventually re-challenged with LPS. The induction of memory was assessed by comparing the response to the LPS challenge of unprimed cells with that of cells primed with bacterial agents and AuNP. The response to LPS was measured as the production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra). While ineffective in directly inducing innate memory per se, and unable to influence LPS-induced tolerance memory, AuNP significantly affected the memory response of BCG-primed cells, by inhibiting the secondary response in terms of both inflammatory and anti-inflammatory factor production. The reprogramming of BCG-induced memory towards a tolerance type of reactivity may open promising perspectives for the use of AuNP in immunomodulatory approaches to autoimmune and chronic inflammatory diseases.
Highlights
Innate immune memory is defined as the ability of innate immune cells to react differently to challenges based on previous stimulations [1,2,3]
The aim of the present study is to investigate whether AuNP are capable of inducing innate immune memory in human monocytes, and/or whether they may modulate memory induced by bacterial agents
Innate immune memory is critical to maintaining successful host defense responses to multiple challenges
Summary
Innate immune memory is defined as the ability of innate immune cells to react differently to challenges based on previous stimulations [1,2,3]. Innate memory is non-specific, but in any case, aimed at developing a better-suited secondary response. More recent evidence has shown that previous challenge with some bacteria, such as the Mycobacterium bovis strain BCG, can induce an innate memory towards an enhanced and more protective secondary response (“trained” immunity) [11,12,13,14]. The protective scavenging role of monocytes/macrophages presents the question of whether and how foreign materials can impact innate immune memory in monocytes and macrophages. This is a critical issue that has to be considered in novel treatments and therapies that use biomedical materials. One class of materials that may have a particular impact on innate memory, because of their particulate nature, are nanomaterials, which have extensive clinical relevance and potential as metal-based imaging agents and as drug or vaccine carriers [19,20]
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