Nanoparticle impact on innate immune cell pattern-recognition receptors and inflammasomes activation

Silva, Ana Luísa; Peres, Carina; Conniot, João; Matos, Ana I.; Moura, Liane I.F.; Carreira, Bárbara; Sainz, Vanessa; Scomparin, Anna; Satchi‐Fainaro, Ronit; Préat, Véronique; Florindo, Helena F.

doi:10.1016/j.smim.2017.09.003

Cited by 68 publications

(59 citation statements)

References 247 publications

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“…These types of toll-like receptors control interferons and cytokines expression and are involved in cellular stress response upon action of exogenous or endogenous ligands, such as bacterial LPS and group of proteins from damage-associated molecular pattern [63]. Data from several sources have identified the activation of TLR2/4 signaling in response to nanoparticles [64,65] or BLM treatment [66]. Litaf was upregulated during acute inflammation phase and had direct links with fibrosis-related genes in CNT and BLM networks for the later time period.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulatory mechanisms of fibrosis development in mouse lung tissue exposed to carbon nanotubes

Zhernovkov

Santra

Cassidy

et al. 2018

Preprint

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BackgroundCarbon nanotubes (CNTs) usage has rapidly increased in the last few decades due to their unique properties, exploited in various industrial and commercial products. Certain types of CNTs cause adverse health effects, including chronic inflammation and fibrosis. Despite the large number of in vitro and in vivo studies evaluating these effects, many important questions remain unanswered due to a lack of mechanistic understanding of how CNTs induce cellular stress responses. In order to predict CNT toxicity, it is important to understand which transcriptional programs are specifically activated in response to CNTs, and what similarities and differences exist in relation to other toxic inducers exerting similar adverse effects. ResultsA systems biology approach was applied to reveal complex interactions at the molecular level in mouse lung tissue in response to different fibrosis inducers: two types of multiwalled CNTs, NM-401 and NRCWE-26, and bleomycin (BLM). Based on mRNA gene expression profiles, we inferred gene regulatory networks (GRNs) to capture functional hierarchical regulatory structures between genes and their regulators. We found that activities of the transcription factors (TFs) Myc, Arid5a and Mxd1 were associated with the regulation of cytokine transcription in response to CNTs, while in response to BLM treatment, Myc was associated with p53 signaling. TF Litaf was identified as the essential regulator for noncanonical signaling of TLR2/4 driven by CNTs. Despite the different nature of the lung injury caused by CNTs and BLM, we identified common stress response modules, that included DNA damage (TFs : E2f8, E2f1, Foxm1), M1/M2 macrophage polarization (TF: Mafb), Interferon response (TFs: Irf7, Stat2 and Irf9) for all agents. ConclusionsThese results suggest that the reconstruction and analysis of TF-centric gene interaction networks can reveal key targets and regulators of cellular stress responses to toxic agents.2

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Section: Discussionmentioning

confidence: 99%

Transcriptional regulatory mechanisms of fibrosis development in mouse lung tissue exposed to carbon nanotubes

Zhernovkov

Santra

Cassidy

et al. 2018

Preprint

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“…While this report did not test TLR activity, a few alternate studies have done so and have shown that both MWCNTs and SWCNTs can activate the TLR2/4-MyD88-NFƙB signaling pathway in macrophages which leads to chemokine secretion (Meng et al 2015;Mukherjee et al 2018). Additionally, noninfectious stimuli from either "self" or the environment, including hydrophobic regions of CNTs, may be categorized as danger-associated molecular patterns (DAMPs), which are involved in the activation of NLR pathways (Silva et al 2017;Mason et al 2012). Interestingly, one study found different profiles of gene expression for TLR signaling, NLR signaling, and downstream signal transduction between CNTs and their depyrogenized versions, indicating the possibility of endotoxin or microbial contamination of CNTs leading to misinterpretation of PRR activation by CNTs (Lahiani et al 2017).…”

Section: Activation Of Pattern Recognition Receptors (Prrs) and Relatmentioning

confidence: 97%

“…Protein corona-coated NMs have been recently termed nanomaterial-associated molecular patterns (NAMPs ). NAMPs have been shown to be directly recognized by PRRs based on their protein composition (Silva et al 2017). Proteins undergoing adsorption to NMs can experience possible conformational and functional changes, leading to altered immune responses to either the NMs or pathogens.…”

Section: Interaction Of Nps With Protein Coronamentioning

confidence: 99%

“…Activation of these receptors, including toll-like receptors (TLRs), C-type lectin receptors (CLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors Fig. 10.2 Diagram showing the interplay of several signaling mechanisms that may be perturbed by NMs and viruses including endosomal PRRs (TLRs) and PRRs that work through the mitochondria (RIG-I-MAVS), inflammasomes, and how ROS may serve as a trigger (RLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and absent in melanoma 2-like receptors (AIM2) (Silva et al 2017;Kawai and Akira 2009), leads to the production and release of IFNs that interrupt viral life cycles by directly interfering with their ability to replicate within an infected host cell. For example, both viral DNA and RNA can be recognized by several PRRs.…”

Section: Activation Of Pattern Recognition Receptors (Prrs) and Relatmentioning

confidence: 99%

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Nanomaterial Effects on Viral Infection

Chen

Humes

Saleh

et al. 2020

Interaction of Nanomaterials With the Immune System

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The potential for environmental and occupational exposures of populations to nanomaterials (NMs) has fostered concerns of associated adverse health effects, with a particular emphasis on pulmonary injury and disease. Many studies have revealed that several types of NMs can evoke a variety of biological responses, such as pulmonary inflammation and oxidative stress, which contribute to allergy, fibrosis, and granuloma formation. Less attention has been paid to health effects that may result from exposure to NMs and additional stressors such as pathogens, with a particular focus on susceptibility to viral infection. This chapter will summarize the current body of literature related to NMs and viral exposures with a primary focus on immune modulation. A summary of the studies performed and major findings to date will be discussed, highlighting proposed molecular mechanisms behind NM-driven host susceptibility, challenges, limitations, and future research needs. Specific mechanisms discussed include direct interaction between NMs and biological molecules, activation of pattern recognition receptors (PRRs) and related signaling pathways, production of oxidative stress and mitochondrial dysfunction, inflammasome activation, and modulation of lipid signaling networks.

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“…Los hay anclados a biomembranas y secretados a circulación. Entre los principales prrs se conocen los tlrs, los receptores tipo Nod (nlrs, por sus siglas en inglés), receptores que unen manosas (mbl, dc-sign, mr) y los receptores lectina tipo-C (clrs, del inglés C-type lectin receptors) (Akira et al, 2006, Demento et al, 2011, Silva et al, 2017. Como muchas otras interacciones biológicas, los receptores de inmunidad innata se unen a sus ligandos mediante interacciones no covalentes.…”

Section: El Sistema Inmune Innato: Un Combate Inmediato Ante El Peligrounclassified

Patrones moleculares asociados a patógenos – ¿héroes o villanos en Nanomedicina?

López-Marı́n

Aguilar

2018

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<p>En nanomedicina, el destino de nanopartículas al interior de un organismo se encuentra fuertemente influenciado por la respuesta del hospedero. Para muchas aplicaciones biomédicas, el reconocimiento de nanopartículas por el sistema inmune constituye uno de los principales problemas: los glóbulos blancos reconocen agentes extraños (incluyendo nanopartículas) y son capaces de destruirlos en el plazo de unos cuantos segundos. Por el contrario, un creciente número de intervenciones terapéuticas se basa en la activación del sistema inmune, cuya disfunción es causa de muchas enfermedades, incluyendo infecciones y cáncer. Mediante la nanotecnología es posible incidir en esta última vertiente, es decir en la activación de la inmunidad. En este artículo se presenta un breve panorama del sistema inmune, con énfasis en una clase de proteínas dedicadas a reconocer microorganismos patógenos de manera inmediata. Las moléculas microbianas reconocidas por dichas proteínas, conocidas como patrones moleculares asociados a patógenos, serán también presentadas. Finalmente, se discutirá la ambivalencia de estas moléculas en la relación nanofármaco-huésped, desde su tradicional figura como factores citotóxicos, a su rol emergente como potentes activadores en el campo de las nanovacunas.</p>

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Nanoparticle impact on innate immune cell pattern-recognition receptors and inflammasomes activation

Cited by 68 publications

References 247 publications

Transcriptional regulatory mechanisms of fibrosis development in mouse lung tissue exposed to carbon nanotubes

Transcriptional regulatory mechanisms of fibrosis development in mouse lung tissue exposed to carbon nanotubes

Nanomaterial Effects on Viral Infection

Patrones moleculares asociados a patógenos – ¿héroes o villanos en Nanomedicina?

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