The Impact of Nanoparticles on Innate Immune Activation by Live Bacteria

Swartzwelter, Benjamin J; Fux, Alexandra C.; Johnson, Litty; Swart, Elmer; Hofer, Sabine; Hofstätter, Norbert; Geppert, Mark; Italiani, Paola; Boraschi, Diana; Duschl, Albert; Himly, Martin

doi:10.3390/ijms21249695

Cited by 25 publications

(14 citation statements)

References 153 publications

(185 reference statements)

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“…This study confirms previous observations that engineered NP can modulate human innate memory (62)(63)(64)(65)(66). A direct capacity of inducing memory, thereby changing the secondary response of human monocytes to a microbial challenge, was observed with AuNP of two different shapes (both coated with citrate and serum proteins), and with iron oxide NP of two different sizes (both coated with the sulfobetaine ZDS and pre-treated with serum).…”

Section: Discussionsupporting

confidence: 90%

“…As general conclusion, we have observed a strongly individual memory response of human innate cells primed with NP, to confirm previous indications (62,64,66). The NP-induced memory response can differ between donors for the same type of NP, a finding that supports the need for a personalised memory profiling, before administration of nanoimaging materials for diagnostic scopes.…”

Section: Discussionsupporting

confidence: 88%

“…In mouse macrophages, pristine graphene could induce a memory profile that resulted in an increased innate/ inflammatory response to subsequent stimulations (62). In human monocytes and macrophages, AuNP could induce memory responses either directly, by priming cells for a different secondary response, or by modulating the memoryinducing capacity of strong stimuli such as LPS (which induces tolerance) and BCG (the Mycobacterium bovis strain used as tuberculosis vaccine, which induces a potentiated secondary responses) (63)(64)(65)(66)(67). Thus, in this study we have focused on the ability of FeOxNP and AuNP of different sizes and shapes not only to induce a primary innate response (measured as balance between the induction of inflammatory vs. anti-inflammatory cytokines) but in particular to induce and/or modulate innate memory.…”

Section: Introductionmentioning

confidence: 99%

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Personalised Profiling of Innate Immune Memory Induced by Nano-Imaging Particles in Human Monocytes

et al. 2021

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Engineered nanoparticles used for medical purposes must meet stringent safety criteria, which include immunosafety, i.e., the inability to activate possibly detrimental immune/inflammatory effects. Even medical nanomaterials devoid of direct immunotoxic or inflammatory effects may have an impact on human health if able to modify innate memory, which is the ability to “prime” future immune responses towards a different, possibly more detrimental reactivity. Although innate memory is usually protective, anomalous innate memory responses may be at the basis of immune pathologies. In this study, we have examined the ability of two nanomaterials commonly used for diagnostic imaging purposes, gold and iron oxide nanoparticles, to induce or modulate innate memory, using an in vitro model based on human primary monocytes. Monocytes were exposed in culture to nanoparticles alone or together with the bacterial agent LPS (priming phase/primary response), then rested for six days (extinction phase), and eventually challenged with LPS (memory/secondary response). The memory response to the LPS challenge was measured as changes in the production of inflammatory (TNFα, IL-6) and anti-inflammatory cytokines (IL-10, IL-1Ra), as compared to unprimed monocytes. The results show that both types of nanoparticles can have an effect in the induction of memory, with changes observed in the cytokine production. By comparing nanomaterials of different shapes (spherical vs. rod-shaped gold particles) and different size (17 vs. 22 nm diameter spherical iron oxide particles), it was evident that innate memory could be differentially induced and modulated depending on size, shape and chemical composition. However, the main finding was that the innate memory effect of the particles was strongly donor-dependent, with monocytes from each donor showing a distinct memory profile upon priming with the same particles, thereby making impossible to draw general conclusions on the particle effects. Thus, in order to predict the effect of imaging nanoparticles on the innate memory of patients, a personalised profiling would be required, able to take in consideration the peculiarities of the individual innate immune reactivity.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Personalised Profiling of Innate Immune Memory Induced by Nano-Imaging Particles in Human Monocytes

et al. 2021

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“…The difference in the effect of AuNPs on memory induced by MDP vs. the entire S. aureus bacteria might be ascribed to the different mechanisms of primary cell activation (which then initiate the epigenetic and metabolic reprogramming responsible for the establishment of memory), MDP mainly acting through NOD2 in the cytoplasm after receptor-independent endocytosis/transport through membrane channels (43,44), while the whole bacteria principally interact with the plasma membrane through lipoteichoic acid activation of TLR2, thereby initiating an MyD88-dependent signaling pathway (45,46). The metabolic cost and pathway involvement of bacterial phagocytosis compared to uptake of soluble factors most likely also contribute to the different memory profiles generated by S. aureus and MDP, although this remains unstudied to date (47). Thus, the presence of AuNPs, which are endocytosed, may have interfered with the MDP-dependent mechanism of memory generation, while unable to affect the memory mechanisms initiated extracellularly by S. aureus.…”

Section: Particulate Microbial Stimulimentioning

confidence: 99%

Innate Memory Reprogramming by Gold Nanoparticles Depends on the Microbial Agents That Induce Memory

et al. 2021

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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.

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“…PLGA is a composite polymer, and metal oxides combined with the formation of nanocomposite have an antibacterial effect. It can deliver multiple molecules simultaneously as a carrier and has been approved by the European Medicines Agency and the US Food and Drug Administration as a drug delivery system (Swartzwelter et al, 2020). Its mechanism is to destroy the integrity of the cell membrane, and it has good antibacterial activity against both Gram-positive bacteria (Staph.…”

Section: O N L I N E I R S T a R T I C L Ementioning

confidence: 99%

Insecticidal Potential of Botanicals from Red Seaweeds against Stored Grain Pests, Rice Weevil (Sitophilus oryzae L.) and Cowpea Weevil (Callosobruchus maculatus Fab.)

Bibi¹,

Tariq²,

Abdelgaleil³

et al. 2022

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The Impact of Nanoparticles on Innate Immune Activation by Live Bacteria

Cited by 25 publications

References 153 publications

Personalised Profiling of Innate Immune Memory Induced by Nano-Imaging Particles in Human Monocytes

Personalised Profiling of Innate Immune Memory Induced by Nano-Imaging Particles in Human Monocytes

Innate Memory Reprogramming by Gold Nanoparticles Depends on the Microbial Agents That Induce Memory

Insecticidal Potential of Botanicals from Red Seaweeds against Stored Grain Pests, Rice Weevil (Sitophilus oryzae L.) and Cowpea Weevil (Callosobruchus maculatus Fab.)

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