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Mechanisms of Innate Immune Activation and Regulation in Health and Disease

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 (31 May 2022) | Viewed by 32606

Special Issue Editors

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
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,

Besides representing the first line of defence 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 observed in the context of the current 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:

  1. Identification and characterization of novel PAMPs and DAMPs
  2. PRR mutations and dysregulation of the immune response
  3. Mechanisms of infectious and sterile innate immune activation
  4. Mechanisms fuelling non-resolving inflammation
  5. Mechanisms of inflammation-dependent tissue damage
  6. Anti-inflammatory properties of old and new drugs
  7. Novel targets for old and new drugs to control hyperinflammation
  8. 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

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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 (11 papers)

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Research

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13 pages, 1887 KiB  
Article
Inhibition of Class I Histone Deacetylase Activity Blocks the Induction of TNFAIP3 Both Directly and Indirectly via the Suppression of Endogenous TNF-α
by Tiziana Schioppa, Hoang Oanh Nguyen, Laura Tiberio, Francesca Sozio, Carolina Gaudenzi, Mauro Passari, Annalisa Del Prete, Daniela Bosisio and Valentina Salvi
Int. J. Mol. Sci. 2022, 23(17), 9752; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179752 - 28 Aug 2022
Viewed by 1460
Abstract
Histone deacetylase inhibitors (HDIs) are promising drugs for the treatment of inflammatory diseases. However, their therapeutical exploitation is slowed down by severe adverse manifestations that can hardly be foreseen, mainly due to incomplete knowledge of how HDIs impact the delicate balance of inflammatory [...] Read more.
Histone deacetylase inhibitors (HDIs) are promising drugs for the treatment of inflammatory diseases. However, their therapeutical exploitation is slowed down by severe adverse manifestations that can hardly be foreseen, mainly due to incomplete knowledge of how HDIs impact the delicate balance of inflammatory mediators. In this work, we characterized the effects of the HDI trichostatin A (TSA) on the expression of TNFAIP3, which is a crucial inhibitor of the classical NF-kB pathway and an LPS-induced negative feedback regulator. The accumulation of TNFAIP3 mRNA after LPS stimulation showed biphasic behavior, with one wave within the first hour of stimulation and a second wave several hours later, which were both reduced by TSA. By using inhibition and knockdown approaches, we identified two temporally and mechanistically distinct modes of action. The first wave of TNAIP3 accumulation was directly blunted by the histone deacetylase (HDAC) blockade. By contrast, the second wave was decreased mainly because of the lack of endogenous TNF-α induction, which, in turn, depended on the intact HDAC activity. In both cases, class I HDACs appeared to play a nonredundant role, with HDAC3 required, but not sufficient, for TNF-α and TNFAIP3 induction. In addition to TNFAIP3, TNF-α is known to induce many response genes that orchestrate the inflammatory cascade. Thus, suppression of TNF-α may represent a general mechanism through which HDIs regulate a selected set of target genes. Full article
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15 pages, 2216 KiB  
Article
The PDE4 Inhibitor Tanimilast Restrains the Tissue-Damaging Properties of Human Neutrophils
by Tiziana Schioppa, Hoang Oanh Nguyen, Valentina Salvi, Norma Maugeri, Fabrizio Facchinetti, Gino Villetti, Maurizio Civelli, Carolina Gaudenzi, Mauro Passari, Francesca Sozio, Ilaria Barbazza, Nicola Tamassia, Marco A. Cassatella, Annalisa Del Prete, Daniela Bosisio and Laura Tiberio
Int. J. Mol. Sci. 2022, 23(9), 4982; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094982 - 29 Apr 2022
Cited by 5 | Viewed by 2311
Abstract
Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001—is a novel inhaled [...] Read more.
Neutrophils, the most abundant subset of leukocytes in the blood, play a pivotal role in host response against invading pathogens. However, in respiratory diseases, excessive infiltration and activation of neutrophils can lead to tissue damage. Tanimilast-international non-proprietary name of CHF6001—is a novel inhaled phosphodiesterase 4 (PDE4) inhibitor in advanced clinical development for the treatment of chronic obstructive pulmonary disease (COPD), a chronic inflammatory lung disease where neutrophilic inflammation plays a key pathological role. Human neutrophils from healthy donors were exposed to pro-inflammatory stimuli in the presence or absence of tanimilast and budesonide—a typical inhaled corticosteroid drug-to investigate the modulation of effector functions including adherence to endothelial cells, granule protein exocytosis, release of extracellular DNA traps, cytokine secretion, and cell survival. Tanimilast significantly decreased neutrophil-endothelium adhesion, degranulation, extracellular DNA traps casting, and cytokine secretion. In contrast, it promoted neutrophil survival by decreasing both spontaneous apoptosis and cell death in the presence of pro-survival factors. The present work suggests that tanimilast can alleviate the severe tissue damage caused by massive recruitment and activation of neutrophils in inflammatory diseases such as COPD. Full article
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19 pages, 4240 KiB  
Article
Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection
by Andrea Olmos-Ortiz, Mayra Hernández-Pérez, Pilar Flores-Espinosa, Gabriela Sedano, Addy Cecilia Helguera-Repetto, Óscar Villavicencio-Carrisoza, María Yolotzin Valdespino-Vazquez, Arturo Flores-Pliego, Claudine Irles, Bruno Rivas-Santiago, Elsa Romelia Moreno-Verduzco, Lorenza Díaz and Verónica Zaga-Clavellina
Int. J. Mol. Sci. 2022, 23(6), 2994; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23062994 - 10 Mar 2022
Cited by 5 | Viewed by 2196
Abstract
An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal–fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides [...] Read more.
An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal–fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as Escherichia coli. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual E. coli infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to E. coli choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live E. coli (1 × 105 CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-α and IL-1β secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that E. coli infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2–4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8–24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period. Full article
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29 pages, 7541 KiB  
Article
Metabolic Pathways Involved in Formation of Spontaneous and Lipopolysaccharide-Induced Neutrophil Extracellular Traps (NETs) Differ in Obesity and Systemic Inflammation
by Iwona Cichon, Weronika Ortmann and Elzbieta Kolaczkowska
Int. J. Mol. Sci. 2021, 22(14), 7718; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147718 - 19 Jul 2021
Cited by 15 | Viewed by 3925
Abstract
Obesity manifests itself with low-grade chronic inflammation that shapes immune responses during infection. Albeit obese individuals are at risk of higher mortality due to comorbidities, they are better protected from systemic inflammation. Recently, we showed that in the vasculature of obese mice kept [...] Read more.
Obesity manifests itself with low-grade chronic inflammation that shapes immune responses during infection. Albeit obese individuals are at risk of higher mortality due to comorbidities, they are better protected from systemic inflammation. Recently, we showed that in the vasculature of obese mice kept on high-fat diet (HFD), neutrophils produce less neutrophil extracellular traps (NETs) than in lean controls (normal diet, ND). NETs are used by neutrophils to counteract severe infection, but they also cause collateral damage. Hardly anything is known about metabolic requirements for their formation, especially in the context of obesity and/or sepsis. Thus, we aimed to study the immunometabolism of NET formation by application of ex vivo neutrophil analyses (Seahorse analyzer, selective inhibitors, confocal imaging) and intravital microscopy. The obtained data show that glycolysis and/or pentose phosphate pathway are involved in NETs release by ND neutrophils in both physiological and inflammatory conditions. In contrast, such cells of septic HFD mice utilize these routes only to spontaneously cast NETs, while after secondary ex vivo activation they exhibit so called “exhausted phenotype”, which manifests itself in diminished NET release despite high glycolytic potential and flexibility to oxidize fatty acids. Moreover, impact of ATP synthase inhibition on NET formation is revealed. Overall, the study shows that the neutrophil potential to cast NETs depends on both the metabolic and inflammatory state of the individual. Full article
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18 pages, 3498 KiB  
Article
IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis
by Tianheng Hou, Miranda Sin-Man Tsang, Lea Ling-Yu Kan, Peiting Li, Ida Miu-Ting Chu, Christopher Wai-Kei Lam and Chun-Kwok Wong
Int. J. Mol. Sci. 2021, 22(14), 7393; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147393 - 09 Jul 2021
Cited by 8 | Viewed by 3578
Abstract
Atopic dermatitis (AD) represents a severe global burden on physical, physiological and mental health. Innate immune cell basophils are essential for provoking allergic inflammation in AD. However, the roles of novel immunoregulatory cytokine IL-37 in basophils remain elusive. We employed in vitro co-culture [...] Read more.
Atopic dermatitis (AD) represents a severe global burden on physical, physiological and mental health. Innate immune cell basophils are essential for provoking allergic inflammation in AD. However, the roles of novel immunoregulatory cytokine IL-37 in basophils remain elusive. We employed in vitro co-culture of human basophils and human keratinocyte HaCaT cells and an in vivo MC903-induced AD murine model to investigate the anti-inflammatory mechanism of IL-37. In the in vitro model, IL-37b significantly decreased Der p1-induced thymic stromal lymphopoietin (TSLP) overexpression in HaCaT cells and decreased the expression of TSLP receptor as well as basophil activation marker CD203c on basophils. IL-37 could also reduce Th2 cytokine IL-4 release from TSLP-primed basophils ex vivo. In the in vivo model, alternative depletion of basophils ameliorated AD symptoms and significantly lowered the Th2 cell and eosinophil populations in the ear and spleen of the mice. Blocking TSLP alleviated the AD-like symptoms and reduced the infiltration of basophils in the spleen. In CRISPR/Cas9 human IL-37b knock-in mice or mice with direct treatment by human IL-37b antibody, AD symptoms including ear swelling and itching were significantly alleviated upon MC903 challenge. Notably, IL-37b presence significantly reduced the basophil infiltration in ear lesions. In summary, IL-37b could regulate the TSLP-mediated activation of basophils and reduce the release of IL-4. The results, therefore, suggest that IL-37 may target TSLP-primed basophils to alleviate AD. Full article
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20 pages, 46113 KiB  
Article
Molecular Mechanisms of ZC3H12C/Reg-3 Biological Activity and Its Involvement in Psoriasis Pathology
by Mateusz Wawro, Jakub Kochan, Weronika Sowinska, Aleksandra Solecka, Karolina Wawro, Agnieszka Morytko, Patrycja Kwiecinska, Beata Grygier, Mateusz Kwitniewski, Mingui Fu, Joanna Cichy and Aneta Kasza
Int. J. Mol. Sci. 2021, 22(14), 7311; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147311 - 07 Jul 2021
Cited by 2 | Viewed by 3162
Abstract
The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members [...] Read more.
The members of the ZC3H12/MCPIP/Regnase family of RNases have emerged as important regulators of inflammation. In contrast to Regnase-1, -2 and -4, a thorough characterization of Regnase-3 (Reg-3) has not yet been explored. Here we demonstrate that Reg-3 differs from other family members in terms of NYN/PIN domain features, cellular localization pattern and substrate specificity. Together with Reg-1, the most comprehensively characterized family member, Reg-3 shared IL-6, IER-3 and Reg-1 mRNAs, but not IL-1β mRNA, as substrates. In addition, Reg-3 was found to be the only family member which regulates transcript levels of TNF, a cytokine implicated in chronic inflammatory diseases including psoriasis. Previous meta-analysis of genome-wide association studies revealed Reg-3 to be among new psoriasis susceptibility loci. Here we demonstrate that Reg-3 transcript levels are increased in psoriasis patient skin tissue and in an experimental model of psoriasis, supporting the immunomodulatory role of Reg-3 in psoriasis, possibly through degradation of mRNA for TNF and other factors such as Reg-1. On the other hand, Reg-1 was found to destabilize Reg-3 transcripts, suggesting reciprocal regulation between Reg-3 and Reg-1 in the skin. We found that either Reg-1 or Reg-3 were expressed in human keratinocytes in vitro. However, in contrast to robustly upregulated Reg-1 mRNA levels, Reg-3 expression was not affected in the epidermis of psoriasis patients. Taken together, these data suggest that epidermal levels of Reg-3 are negatively regulated by Reg-1 in psoriasis, and that Reg-1 and Reg-3 are both involved in psoriasis pathophysiology through controlling, at least in part different transcripts. Full article
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13 pages, 1827 KiB  
Article
Molecular Basis for the Activation of Human Innate Immune Response by the Flagellin Derived from Plant-Pathogenic Bacterium, Acidovorax avenae
by Nasir Javaid, Hiroyuki Hirai, Fang-Sik Che and Sangdun Choi
Int. J. Mol. Sci. 2021, 22(13), 6920; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136920 - 28 Jun 2021
Cited by 1 | Viewed by 1922
Abstract
Acidovorax avenae is a flagellated, pathogenic bacterium to various plant crops that has also been found in human patients with haematological malignancy, fever, and sepsis; however, the exact mechanism for infection in humans is not known. We hypothesized that the human innate immune [...] Read more.
Acidovorax avenae is a flagellated, pathogenic bacterium to various plant crops that has also been found in human patients with haematological malignancy, fever, and sepsis; however, the exact mechanism for infection in humans is not known. We hypothesized that the human innate immune system could be responsive to the purified flagellin isolated from A. avenae, named FLA-AA. We observed the secretion of inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-8 by treating FLA-AA to human dermal fibroblasts, as well as macrophages. This response was exclusively through TLR5, which was confirmed by using TLR5-overexpression cell line, 293/hTLR5, as well as TLR5-specific inhibitor, TH1020. We also observed the secretion of inflammatory cytokine, IL-1β, by the activation of NLRC4 with FLA-AA. Overall, our results provide a molecular basis for the inflammatory response caused by FLA-AA in cell-based assays. Full article
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14 pages, 2822 KiB  
Article
Grouper TRAF4, a Novel, CP-Interacting Protein That Promotes Red-Spotted Grouper Nervous Necrosis Virus Replication
by Siting Wu, Mengshi Sun, Xin Zhang, Jiaming Liao, Mengke Liu, Qiwei Qin and Jingguang Wei
Int. J. Mol. Sci. 2021, 22(11), 6136; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22116136 - 07 Jun 2021
Cited by 10 | Viewed by 2087
Abstract
Tumor necrosis factor receptor-associated factors (TRAFs) play important roles in the biological processes of immune regulation, the inflammatory response, and apoptosis. TRAF4 belongs to the TRAF family and plays a major role in many biological processes. Compared with other TRAF proteins, the functions [...] Read more.
Tumor necrosis factor receptor-associated factors (TRAFs) play important roles in the biological processes of immune regulation, the inflammatory response, and apoptosis. TRAF4 belongs to the TRAF family and plays a major role in many biological processes. Compared with other TRAF proteins, the functions of TRAF4 in teleosts have been largely unknown. In the present study, the TRAF4 homologue (EcTRAF4) of the orange-spotted grouper was characterized. EcTRAF4 consisted of 1413 bp encoding a 471-amino-acid protein, and the predicted molecular mass was 54.27 kDa. EcTRAF4 shares 99.79% of its identity with TRAF4 of the giant grouper (E. lanceolatus). EcTRAF4 transcripts were ubiquitously and differentially expressed in all the examined tissues. EcTRAF4 expression in GS cells was significantly upregulated after stimulation with red-spotted grouper nervous necrosis virus (RGNNV). EcTRAF4 protein was distributed in the cytoplasm of GS cells. Overexpressed EcTRAF4 promoted RGNNV replication during viral infection in vitro. Yeast two-hybrid and coimmunoprecipitation assays showed that EcTRAF4 interacted with the coat protein (CP) of RGNNV. EcTRAF4 inhibited the activation of IFN3, IFN-stimulated response element (ISRE), and nuclear factor-κB (NF-κB). Overexpressed EcTRAF4 also reduced the expression of interferon (IFN)-related molecules and pro-inflammatory factors. Together, these results demonstrate that EcTRAF4 plays crucial roles in RGNNV infection. Full article
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Review

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18 pages, 730 KiB  
Review
Activation of Innate Immunity by Therapeutic Nucleic Acids
by Ali Bishani and Elena L. Chernolovskaya
Int. J. Mol. Sci. 2021, 22(24), 13360; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222413360 - 12 Dec 2021
Cited by 13 | Viewed by 3576
Abstract
Nucleic acid-based therapeutics have gained increased attention during recent decades because of their wide range of application prospects. Immunostimulatory nucleic acids represent a promising class of potential drugs for the treatment of tumoral and viral diseases due to their low toxicity and stimulation [...] Read more.
Nucleic acid-based therapeutics have gained increased attention during recent decades because of their wide range of application prospects. Immunostimulatory nucleic acids represent a promising class of potential drugs for the treatment of tumoral and viral diseases due to their low toxicity and stimulation of the body’s own innate immunity by acting on the natural mechanisms of its activation. The repertoire of nucleic acids that directly interact with the components of the immune system is expanding with the improvement of both analytical methods and methods for the synthesis of nucleic acids and their derivatives. Despite the obvious progress in this area, the problem of delivering therapeutic acids to target cells as well as the unresolved issue of achieving a specific therapeutic effect based on activating the mechanism of interferon and anti-inflammatory cytokine synthesis. Minimizing the undesirable effects of excessive secretion of inflammatory cytokines remains an unsolved task. This review examines recent data on the types of immunostimulatory nucleic acids, the receptors interacting with them, and the mechanisms of immunity activation under the action of these molecules. Finally, data on immunostimulatory nucleic acids in ongoing and completed clinical trials will be summarized. Full article
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21 pages, 1218 KiB  
Review
Signals and Mechanisms Regulating Monocyte and Macrophage Activation in the Pathogenesis of Juvenile Idiopathic Arthritis
by Chao-Yi Wu, Huang-Yu Yang, Jing-Long Huang and Jenn-Haung Lai
Int. J. Mol. Sci. 2021, 22(15), 7960; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22157960 - 26 Jul 2021
Cited by 8 | Viewed by 3058
Abstract
Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many autoimmune diseases. In addition, they display immunoregulatory effects that impact inflammation and are essential in tissue repair and [...] Read more.
Monocytes (Mos) and macrophages (Mφs) are key players in the innate immune system and are critical in coordinating the initiation, expansion, and regression of many autoimmune diseases. In addition, they display immunoregulatory effects that impact inflammation and are essential in tissue repair and regeneration. Juvenile idiopathic arthritis (JIA) is an umbrella term describing inflammatory joint diseases in children. Accumulated evidence suggests a link between Mo and Mφ activation and JIA pathogenesis. Accordingly, topics regarding the signals and mechanisms regulating Mo and Mφ activation leading to pathologies in patients with JIA are of great interest. In this review, we critically summarize recent advances in the understanding of how Mo and Mφ activation is involved in JIA pathogenesis and focus on the signaling pathways and mechanisms participating in the related cell activation processes. Full article
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11 pages, 255 KiB  
Review
PIMS-TS, the New Paediatric Systemic Inflammatory Disease Related to Previous Exposure to SARS-CoV-2 Infection—“Rheumatic Fever” of the 21st Century?
by Violetta Opoka-Winiarska, Ewelina Grywalska and Jacek Roliński
Int. J. Mol. Sci. 2021, 22(9), 4488; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094488 - 26 Apr 2021
Cited by 10 | Viewed by 3950
Abstract
Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) is a new systemic inflammatory disease that mainly affects children. Its course in many features resembles that of acute rheumatic fever (ARF). Therefore, it is interesting [...] Read more.
Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) is a new systemic inflammatory disease that mainly affects children. Its course in many features resembles that of acute rheumatic fever (ARF). Therefore, it is interesting that the experiences with ARF can be used in the management of patients with PIMS-TS. The aim of the article is to analyse the current data on PIMS-TS in relation to ARF. PIMS-TS and ARF are associated with an abnormal immune response to specific pathogens (SARS-CoV-2 and group A streptococcus, respectively). The main symptoms of both diseases are fever and cardiac involvement. Current therapy for PIMS-TS is based on anti-inflammatory treatment: intravenous immunoglobulin (first-line), intravenous glucocorticoids (second-line), or biological therapy (third-line; including interleukin [IL]-1 antagonists, IL-6 receptor blockers, and anti-tumour necrosis factor agents). Vaccination might be good prophylaxis, but the efficacy and safety of the vaccines against SARS-CoV-2 have not yet been established in children. Interesting insights may be gained by considering PIMS-TS in light of what is known of ARF due to their similar courses, but there are still many unanswered questions surrounding this disease and its pathogenesis. Full article
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