Gold nanoparticles (AuNPs) impair LPS-driven immune responses by promoting a tolerogenic-like dendritic cell phenotype with altered endosomal structures.

Sara Michelini,Francesco Barbero,Alessandra Prinelli,Damjana Drobne,Jutta Horejs-Hoeck,Philip Steiner,Victor F Puntes,Thomas Verwanger,Albert Duschl,Richard Weiss,Ursula Lütz-Meindl,Ancuela Andosch

doi:10.1039/d0nr09153g

Abstract

Dendritic cells (DCs) shape immune responses by influencing T-cell activation. Thus, they are considered both an interesting model for studying nano-immune interactions and a promising target for nano-based biomedical applications. However, the accentuated ability of nanoparticles (NPs) to interact with biomolecules may have an impact on DC function that poses an unexpected risk of unbalanced immune reactions. Here, we investigated the potential effects of gold nanoparticles (AuNPs) on DC function and the consequences for effector and memory T-cell responses in the presence of the microbial inflammatory stimulus lipopolysaccharide (LPS). Overall, we found that, in the absence of LPS, none of the tested NPs induced a DC response. However, whereas 4-, 8-, and 11 nm AuNPs did not modulate LPS-dependent immune responses, 26 nm AuNPs shifted the phenotype of LPS-activated DCs toward a tolerogenic state, characterized by downregulation of CD86, IL-12 and IL-27, upregulation of ILT3, and induction of class E compartments. Moreover, this DC phenotype was less proficient in promoting Th1 activation and central memory T-cell proliferation. Taken together, these findings support the perception that AuNPs are safe under homeostatic conditions; however, particular care should be taken in patients experiencing a current infection or disorders of the immune system.

Highlights

The human immune system can be divided in two branches: the innate and the adaptive immune system
As reported by other authors, the majority of immune responses to nanomaterials (NMs) are characterized by an adaptation process resulting in silent elimination of the NM or transient inflammation followed by full resolution.[1]
Since the reactivity of NPs is strongly influenced by their composition, size, charge, shape, and aggregation status, it is of outmost importance to carry out a comprehensive characterization of NMs used in biological studies

Summary

Introduction

The human immune system can be divided in two branches: the innate and the adaptive immune system. Innate immune responses are usually followed by activation of the adaptive immune system, which is capable of mounting a pathogen-specific response mediated by T cells and B cells. Paper (Tregs) have the crucial role of suppressing excessive inflammation and autoimmunity.[5,6,7,8,9,10,11] unbalanced Th cell polarization and activation is often linked to immune-related pathologies.[12,13] Interestingly, each of these Th cell subsets, known as effector T cells, can be identified using specific molecular markers such as cytokines and surface markers.[11] While many effector T cells die during pathogen clearance, a specific Th cell population termed “memory cells” remains poised for years and decades and is crucial for establishing long-term protection.[14,15]

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