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Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2)

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Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 12824

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Special Issue Editors

Dr. Daniela Bosisio

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Guest Editor

Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
Interests: dendritic cells; TLRs, miRNAs; extracellular vesicles; autoinflammation; tumor microenvironment
Special Issues, Collections and Topics in MDPI journals

Dr. Valentina Salvi

E-Mail Website
Guest Editor

Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
Interests: dendritic cells; TLRs; miRNAs; extracellular vesicles; Aicardi-Goutieres Syndrome; psoriasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue follows the publication of the first volume on “Mechanisms of Innate Immune Activation and Regulation in Health and Disease”, which presented more than 10 interesting papers.

Besides representing the first line of defense against invading pathogens, innate immunity also instructs adaptive effectors to mount appropriate, pathogen-tailored responses. Excessive or unwanted activation of innate cells may thus harm the organisms by fostering autoimmunity, non-resolving inflammation, or both. On these premises, understanding the mechanisms of innate immune activation is of pivotal importance to identify new therapeutic targets and strategies to cope with hyperinflammation.

Innate immune cells get activated upon recognition of structural features of classes of pathogens (pathogen-associated molecular patterns, PAMPs) by specific sensors named pattern recognition receptors (PRRs). In addition to PAMPs, PRRs also recognize self-danger signals (damage-associated molecular patterns, DAMPs) that initiate non-infectious (sterile) inflammatory responses. Because of the intrinsic nature of DAMPs, sterile inflammation is a potentially self-renewing phenomenon.

The importance of DAMPs and gain-of-function mutations of PRRs as triggers of autoinflammatory and autoimmune diseases is a prevailing topic of research and discovery. The roles of cytoplasmic DNA in the pathogenesis of Aicardi-Goutières syndrome type I, of the gain-of-function mutation of IFIH1 in Aicardi-Goutières syndrome type 7 and of accumulating self-nucleic acids in complex, multifactorial diseases such as Systemic Lupus Erithematosus and psoriasis are only mere examples of a vivid field of investigation. On the other hand, autoimmune and autoinflammatory manifestations recently observed in the context of the coronavirus disease 2019 (COVID-19) pandemic, such as paediatric inflammatory multisystemic syndrome (PIMS), have potently reaffirmed the strong relationship between PAMPs, non-sterile inflammation and the unleashing of uncontrolled immune responses.

This Special Issue aims to gather original research and review articles dealing with any aspect of controlled or uncontrolled innate immune activation, with a special focus on new molecular targets and therapies to control non-resolving inflammation. Suggested topics:

Identification and characterization of novel PAMPs and DAMPs
PRR mutations and dysregulation of the immune response
Mechanisms of infectious and sterile innate immune activation
Mechanisms fuelling non-resolving inflammation
Mechanisms of inflammation-dependent tissue damage
Anti-inflammatory properties of old and new drugs
Novel targets for old and new drugs to control hyperinflammation
DAMPs as diagnostic and prognostic biomarkers

Pure clinical/investigation studies cannot be considered, but clinical submissions with biomolecular experiments are welcomed.

Dr. Daniela Bosisio
Dr. Valentina Salvi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

autoinflammation
sterile inflammation
damage-associated molecular patterns (DAMPs)
pathogen recognition receptors (PRRs)
pathogen-associated molecular patterns (PAMPs)
self-nucleic acids
retroelements
anti-inflammatory drugs
inflammasome
COVID-19
paediatric inflammatory multisystemic syndrome (PIMS)
molecular mimicry
polyclonal activation
type I Interferons (IFNs)
interferon signature
proinflammatory cytokines
hyperinflammation

Published Papers (5 papers)

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Research

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16 pages, 10608 KiB

Open AccessArticle

The Role of Bacteria–Mitochondria Communication in the Activation of Neuronal Innate Immunity: Implications to Parkinson’s Disease

by João D. Magalhães, Ana Raquel Esteves, Emanuel Candeias, Diana F. Silva, Nuno Empadinhas and Sandra Morais Cardoso

Int. J. Mol. Sci. 2023, 24(5), 4339; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054339 - 22 Feb 2023

Cited by 2 | Viewed by 1930

Abstract

Mitochondria play a key role in regulating host metabolism, immunity and cellular homeostasis. Remarkably, these organelles are proposed to have evolved from an endosymbiotic association between an alphaproteobacterium and a primitive eukaryotic host cell or an archaeon. This crucial event determined that human cell mitochondria share some features with bacteria, namely cardiolipin, N-formyl peptides, mtDNA and transcription factor A, that can act as mitochondrial-derived damage-associated molecular patterns (DAMPs). The impact of extracellular bacteria on the host act largely through the modulation of mitochondrial activities, and often mitochondria are themselves immunogenic organelles that can trigger protective mechanisms through DAMPs mobilization. In this work, we demonstrate that mesencephalic neurons exposed to an environmental alphaproteobacterium activate innate immunity through toll-like receptor 4 and Nod-like receptor 3. Moreover, we show that mesencephalic neurons increase the expression and aggregation of alpha-synuclein that interacts with mitochondria, leading to their dysfunction. Mitochondrial dynamic alterations also affect mitophagy which favors a positive feedback loop on innate immunity signaling. Our results help to elucidate how bacteria and neuronal mitochondria interact and trigger neuronal damage and neuroinflammation and allow us to discuss the role of bacterial-derived pathogen-associated molecular patterns (PAMPs) in Parkinson’s disease etiology. Full article

(This article belongs to the Special Issue Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2))

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14 pages, 2125 KiB

Open AccessArticle

CD14⁺-Monocytes Exposed to Apolipoprotein CIII Express Tissue Factor

by Oliviero Olivieri, Sara Gasperini, Federica Calzetti, Elisa Gardiman, Annalisa Castagna, Nicola Martinelli, Nicola Tamassia and Marco A. Cassatella

Int. J. Mol. Sci. 2023, 24(3), 2223; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24032223 - 22 Jan 2023

Cited by 1 | Viewed by 1464

Abstract

Apolipoprotein CIII (ApoCIII) represents a key regulator of plasma lipid metabolism and a recognized risk factor for atherosclerosis and cardiovascular diseases. Beyond the regulation of lipoprotein trafficking, ApoCIII is also involved in endothelial dysfunction and monocyte recruitment related to atherothrombosis. With tissue factor (TF) being the primary initiator of the blood coagulation cascade, we hypothesized that ApoCIII-treated monocytes could express it. Hence, human CD14⁺-monocytes and autologous neutrophils were incubated with ApoCIII and sera from human subjects containing previously measured ApoCIII amounts. By RT-qPCR and ELISA, CD14⁺-monocytes, but not neutrophils, were found to show increased mRNA expression and production of TNFα, IL-1β and IL-6 as well as TF mRNA once exposed to ultra-purified ApoCIII. By flow cytometry, CD14⁺-monocytes were found to rapidly express TF on their cell surface membrane when incubated with either ApoCIII or sera with known concentrations of ApoCIII. Finally, preincubation with specific ApoCIII-neutralizing antibodies significantly reduced the ability of most sera with known concentrations of ApoCIII to upregulate TF protein, other than partially inhibiting cytokine release, in CD14⁺-monocytes. In sum, herein we demonstrate that ApoCIII activates CD14⁺-monocytes to express TF. The data identify a potential mechanism which links circulating apolipoproteins with inflammation and atherothrombosis-related processes underlying cardiovascular risk. Full article

(This article belongs to the Special Issue Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2))

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Review

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28 pages, 4586 KiB

Open AccessReview

Significance of the cGAS-STING Pathway in Health and Disease

by Jinglin Zhou, Zhan Zhuang, Jiamian Li and Zhihua Feng

Int. J. Mol. Sci. 2023, 24(17), 13316; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241713316 - 28 Aug 2023

Cited by 4 | Viewed by 2371

Abstract

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a significant role in health and disease. In this pathway, cGAS, one of the major cytosolic DNA sensors in mammalian cells, regulates innate immunity and the STING-dependent production of pro-inflammatory cytokines, including type-I interferon. Moreover, the cGAS–STING pathway is integral to other cellular processes, such as cell death, cell senescence, and autophagy. Activation of the cGAS–STING pathway by “self” DNA is also attributed to various infectious diseases and autoimmune or inflammatory conditions. In addition, the cGAS–STING pathway activation functions as a link between innate and adaptive immunity, leading to the inhibition or facilitation of tumorigenesis; therefore, research targeting this pathway can provide novel clues for clinical applications to treat infectious, inflammatory, and autoimmune diseases and even cancer. In this review, we focus on the cGAS–STING pathway and its corresponding cellular and molecular mechanisms in health and disease. Full article

(This article belongs to the Special Issue Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2))

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31 pages, 2598 KiB

Open AccessReview

Immunomodulatory Role of Interferons in Viral and Bacterial Infections

by Paulina Mertowska, Konrad Smolak, Sebastian Mertowski and Ewelina Grywalska

Int. J. Mol. Sci. 2023, 24(12), 10115; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241210115 - 14 Jun 2023

Cited by 9 | Viewed by 2741

Abstract

Interferons are a group of immunomodulatory substances produced by the human immune system in response to the presence of pathogens, especially during viral and bacterial infections. Their remarkably diverse mechanisms of action help the immune system fight infections by activating hundreds of genes involved in signal transduction pathways. In this review, we focus on discussing the interplay between the IFN system and seven medically important and challenging viruses (herpes simplex virus (HSV), influenza, hepatitis C virus (HCV), lymphocytic choriomeningitis virus (LCMV), human immunodeficiency virus (HIV), Epstein–Barr virus (EBV), and SARS-CoV coronavirus) to highlight the diversity of viral strategies. In addition, the available data also suggest that IFNs play an important role in the course of bacterial infections. Research is currently underway to identify and elucidate the exact role of specific genes and effector pathways in generating the antimicrobial response mediated by IFNs. Despite the numerous studies on the role of interferons in antimicrobial responses, many interdisciplinary studies are still needed to understand and optimize their use in personalized therapeutics. Full article

(This article belongs to the Special Issue Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2))

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14 pages, 965 KiB

Open AccessReview

Role of Damage-Associated Molecular Patterns (DAMPS) in the Postoperative Period after Colorectal Surgery

by María José Caballero-Herrero, Esther Jumilla, Manuel Buitrago-Ruiz, Graciela Valero-Navarro and Santiago Cuevas

Int. J. Mol. Sci. 2023, 24(4), 3862; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24043862 - 15 Feb 2023

Cited by 3 | Viewed by 3696

Abstract

Anastomotic leakage (AL) is a defect of the intestinal wall at the anastomotic site and is one of the most severe complications in colorectal surgery. Previous studies have shown that the immune system response plays a significant role in the development of AL. In recent years, DAMPs (damage-associated molecular patterns) have been identified as cellular compounds with the ability to activate the immune system. The NLRP3 inflammasome plays an important role in the inflammatory responses which are mediated by DAMPs such as ATP, HSP proteins or uric acid crystals, when found in extracellular environments. Recent publications suggest that systemic concentration of DAMPs in patients with colorectal surgery may determine the inflammatory process and have a role in the occurrence of AL and other post-surgery complications. This review provides valuable knowledge about the current evidence supporting this hypothesis and highlights the possible role of these compounds in postoperative processes, which could open a new path to explore new strategies to prevent possible post-surgical complications. Full article

(This article belongs to the Special Issue Mechanisms of Innate Immune Activation and Regulation in Health and Disease (Volume 2))

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