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Cellular Signalling Pathways in Innate Immunity
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Cellular Signalling Pathways in Innate Immunity

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 October 2022) | Viewed by 10887

Special Issue Editor

Dr. Dominic De Nardo

E-Mail Website
Guest Editor
Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
Interests: innate immunity; inflammation; pattern recognition receptors (PRRs); STING; cGAS; TLRs; inflammasomes; signalling pathways

Special Issue Information

Dear Colleagues,

A unifying principle of life is that all organisms possess a physiological response to danger. The innate immune system is conserved through more that 600 million years of evolution to mediate host defence. A large family of pattern recognition receptors (PRRs) comprise the innate immune system of surveillance proteins that recognise foreign microbial molecules, mislocalised host molecules and cellular perturbations to stimulate physiological inflammatory processes to clear infection and/or restore cellular homeostasis. Downstream of active PRRs are networks of intricately controlled signalling pathways that coordinate a tailored transcriptionally or proteolytically mediated immune response. Not surprisingly, aberrations in innate immune signalling lead to rampant inflammation that is implicated in a plethora of pathological conditions including, autoimmunity, autoinflammation, cancer, metabolic disorders and neuroinflammation. This special issue "Cellular signalling pathways in innate immunity", aims to explore recent advances in the field, inviting original research articles and reviews, with a focus on the underlying molecular mechanisms controlling innate immune responses during host defence and in disease progression.

Dr. Dominic De Nardo
Guest Editor

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

  • innate immunity
  • pattern recognition receptors
  • toll-like receptors
  • cGAS-STING inflammasomes
  • RIG-I-like receptors
  • signal transduction
  • inflammation

Published Papers (6 papers)

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Research

14 pages, 3096 KiB  
Article
Immunopathological Mechanisms of Bird-Related Hypersensitivity Pneumonitis
by Silvia Sánchez-Díez, María Jesús Cruz, Miquel de Homdedeu, Iñigo Ojanguren, Christian Romero-Mesones, Irene Sansano and Xavier Muñoz
Int. J. Mol. Sci. 2023, 24(3), 2884; https://doi.org/10.3390/ijms24032884 - 2 Feb 2023
Viewed by 1506
Abstract
Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins. The immunopathological pathways involved in the disease are still unknown. This study assesses the cellular immune response and the cytokine pattern in a mouse model of BRHP. On days −3 [...] Read more.
Bird-related hypersensitivity pneumonitis (BRHP) is an interstitial lung disease induced by avian proteins. The immunopathological pathways involved in the disease are still unknown. This study assesses the cellular immune response and the cytokine pattern in a mouse model of BRHP. On days −3 and −1, mice were intraperitoneally sensitized with commercial pigeon serum (PS) or saline. Intranasal instillations with PS or saline were carried out on three consecutive days/week over either 3 weeks (Group 1) or 12 weeks (Group 2). Leukocyte and cytokine patterns in lung tissue and pulmonary inflammation in bronchoalveolar lavage (BAL) were analysed. Both groups presented increases in resident monocytes, interstitial macrophages and type 2 dendritic cells (DCs), but also reductions in inflammatory monocytes, alveolar macrophages and tolerogenic DCs compared with their control groups. Group 1 had increased levels of eosinophils and T cells with reductions in neutrophils and B cells, while Group 2 showed high levels of B cells. Both groups exhibited increases in Th1 and Th2 cytokines. Group 2 also showed increased levels of IL-23, a Th17 cytokine. Increased levels of neutrophils, eosinophils and lymphocytes were observed in BAL samples of both groups compared with controls. In the first stages of BRHP, there is a mixed Th1/Th2 immune response, while during the progression of the disease, although there is a Th1 response, the cytokine levels seem to indicate a switch towards a Th2/Th17 mixed response. Full article
(This article belongs to the Special Issue Cellular Signalling Pathways in Innate Immunity)
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11 pages, 3839 KiB  
Communication
Quantifying the Detrimental Effects of Multiple Freeze/Thaw Cycles on Primary Human Lymphocyte Survival and Function
by Valentina Serra, Edoardo Fiorillo, Francesco Cucca and Valeria Orrù
Int. J. Mol. Sci. 2023, 24(1), 634; https://doi.org/10.3390/ijms24010634 - 30 Dec 2022
Cited by 2 | Viewed by 1968
Abstract
The use of cryopreserved peripheral blood mononuclear cells is common in biological research. It is widely accepted that primary cells are rendered unusable by several freezing cycles, although this practice might be very helpful when the biological material is valuable and its re-collection [...] Read more.
The use of cryopreserved peripheral blood mononuclear cells is common in biological research. It is widely accepted that primary cells are rendered unusable by several freezing cycles, although this practice might be very helpful when the biological material is valuable and its re-collection is impractical. To determine the extent to which primary cells undergoing repeated freezing cycles are comparable to one another and to fresh samples, we evaluated overall lymphocyte viability, their proliferation and cytokine production capabilities, as well as the levels of 27 cell subtypes in ten human peripheral blood mononuclear cells frozen for five years and repeatedly thawed. As expected, we observed a progressive increase in cell death percentages on three rounds of thawing, but the frequency of the main lymphocyte subsets was stable across the three thawings. Nevertheless, we observed a significant reduction of B cell frequency in frozen samples compared to fresh ones. On repeated thawings and subsequent conventional stimulation, lymphocyte proliferation significantly decreased, and IL-10, IL-6, GM-CSF, IFN-gamma, and IL-8 showed a trend to lower values. Full article
(This article belongs to the Special Issue Cellular Signalling Pathways in Innate Immunity)
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17 pages, 4603 KiB  
Article
Artemisia gmelinii Extract Alleviates Allergic Airway Inflammation via Balancing TH1/TH2 Homeostasis and Inhibiting Mast Cell Degranulation
by Thi Van Nguyen, Chun Hua Piao, Yan Jing Fan, Zhen Nan Yu, So-Young Lee, Chang Ho Song, Hee Soon Shin and Ok Hee Chai
Int. J. Mol. Sci. 2022, 23(23), 15377; https://doi.org/10.3390/ijms232315377 - 6 Dec 2022
Cited by 8 | Viewed by 2059
Abstract
A new terminology “combined allergic rhinitis and asthma syndrome (CARAS)” was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell [...] Read more.
A new terminology “combined allergic rhinitis and asthma syndrome (CARAS)” was introduced to describe patients suffering from both allergic rhinitis (AR) and asthma. The pathogenesis of allergic airway inflammation has been well known, with the main contribution of TH1/TH2 imbalance and mast cell degranulation. Artemisia gmelinii has been used as an herbal medicine with its hepaprotective, anti-inflammatory, and antioxidant properties. In this study, the effect of A. gmelinii extracts (AGE) on the ovalbumin (OVA)-induced CARAS mouse model was investigated. AGE administration significantly alleviated the nasal rubbing and sneezing, markedly down-regulated both OVA-specific IgE, IgG1, and histamine levels, and up-regulated OVA-specific IgG2a in serum. The altered histology of nasal and lung tissues of CARAS mice was effectively ameliorated by AGE. The AGE treatment group showed markedly increased levels of the TH1 cytokine interleukin (IL)-12 and TH1 transcription factor T-bet. In contrast, the levels of the TH2 cytokines, including IL-4, IL-5, IL-13, and the TH2 transcription factor GATA-3, were notably suppressed by AGE. Moreover, AGE effectively prevented mast cell degranulation in vitro and mast cell infiltration in lung tissues in vivo. Based on these results, we suggest that AGE could be a potential therapeutic agent in OVA-induced CARAS by virtue of its role in balancing the TH1/TH2 homeostasis and inhibiting the mast cell degranulation. Full article
(This article belongs to the Special Issue Cellular Signalling Pathways in Innate Immunity)
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22 pages, 7640 KiB  
Article
Functional Characterization of Largemouth Bass (Micropterus salmoides) Soluble FcγR Homolog in Response to Bacterial Infection
by Jing Wu, Yanping Ma, Yifan Nie, Jingya Wang, Guoqing Feng, Le Hao, Wen Huang, Yugu Li and Zhenxing Liu
Int. J. Mol. Sci. 2022, 23(22), 13788; https://doi.org/10.3390/ijms232213788 - 9 Nov 2022
Cited by 1 | Viewed by 1296
Abstract
Fc receptors (FcRs) are key players in antibody-dependent cellular phagocytosis (ADCP) with their specific recognition of the Fc portion of an immunoglobulin. Despite reports of FcγR-mediated phagocytosis in mammals, little is known about the effects of soluble FcγRs on the immune response. In [...] Read more.
Fc receptors (FcRs) are key players in antibody-dependent cellular phagocytosis (ADCP) with their specific recognition of the Fc portion of an immunoglobulin. Despite reports of FcγR-mediated phagocytosis in mammals, little is known about the effects of soluble FcγRs on the immune response. In this study, FcγRIα was cloned from the largemouth bass (Micropterus salmoides) (MsFcγRIα). Without a transmembrane segment or a cytoplasmic tail, MsFcγRIα was identified as a soluble form protein and widely distributed in the spleen, head kidney, and intestine. The native MsFcγRIα was detected in the serum of Nocardia seriolae-infected largemouth bass and the supernatants of transfected HEK293 cells. Additionally, it was verified that the transfected cells’ surface secreted MsFcRIα could bind to largemouth bass IgM. Moreover, the expression changes of MsFcγRIα, Syk, and Lyn indicated that MsFcγRIα was engaged in the acute phase response to bacteria, and the FcγR-mediated phagocytosis pathway was activated by Nocardia seriolae stimulation. Furthermore, recombinant MsFcγRIα could enhance both reactive oxygen species (ROS) and phagocytosis to Nocardia seriolae of leukocytes, presumably through the interaction of MsFcγRIα with a complement receptor. In conclusion, these findings provided a better understanding of the function of soluble FcγRs in the immune response and further shed light on the mechanism of phagocytosis in teleosts. Full article
(This article belongs to the Special Issue Cellular Signalling Pathways in Innate Immunity)
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16 pages, 2989 KiB  
Article
Distinct Transcriptional Profile of PDZ Genes after Activation of Human Macrophages and Dendritic Cells
by Jorge Rosas-García, Lucero A. Ramón-Luing, Karen Bobadilla, Marco Antonio Meraz-Ríos, Edgar E. Sevilla-Reyes and Teresa Santos-Mendoza
Int. J. Mol. Sci. 2022, 23(13), 7010; https://doi.org/10.3390/ijms23137010 - 24 Jun 2022
Cited by 1 | Viewed by 1550
Abstract
The PDZ (PSD95, Dlg and ZO-1) genes encode proteins that primarily function as scaffolds of diverse signaling pathways. To date, 153 PDZ genes have been identified in the human genome, most of which have multiple protein isoforms widely studied in epithelial and neural [...] Read more.
The PDZ (PSD95, Dlg and ZO-1) genes encode proteins that primarily function as scaffolds of diverse signaling pathways. To date, 153 PDZ genes have been identified in the human genome, most of which have multiple protein isoforms widely studied in epithelial and neural cells. However, their expression and function in immune cells have been poorly studied. Herein, we aimed to assess the transcriptional profiles of 83 PDZ genes in human macrophages (Mɸ) and dendritic cells (DCs) and changes in their relative expression during cell PRR stimulation. Significantly distinct PDZ gene transcriptional profiles were identified under different stimulation conditions. Furthermore, a distinct PDZ gene transcriptional signature was found in Mɸ and DCs under the same phagocytic stimuli. Notably, more than 40 PDZ genes had significant changes in expression, with potentially relevant functions in antigen-presenting cells (APCs). Given that several PDZ proteins are targeted by viral products, our results support that many of these proteins might be viral targets in APCs as part of evasion mechanisms. Our results suggest a distinct requirement for PDZ scaffolds in Mɸ and DCs signaling pathways activation. More assessments on the functions of PDZ proteins in APCs and their role in immune evasion mechanisms are needed. Full article
(This article belongs to the Special Issue Cellular Signalling Pathways in Innate Immunity)
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14 pages, 2718 KiB  
Article
Towards Understanding PRPS1 as a Molecular Player in Immune Response in Yellow Drum (Nibea albiflora)
by Qianqian Tian, Wanbo Li, Jiacheng Li, Yao Xiao, Baolan Wu, Zhiyong Wang and Fang Han
Int. J. Mol. Sci. 2022, 23(12), 6475; https://doi.org/10.3390/ijms23126475 - 9 Jun 2022
Cited by 6 | Viewed by 1892
Abstract
Phosphoribosyl pyrophosphate synthetases (EC 2.7.6.1) are key enzymes in the biological synthesis of phosphoribosyl pyrophosphate and are involved in diverse developmental processes. In our previous study, the PRPS1 gene was discovered as a key disease-resistance candidate gene in yellow drum, Nibea albiflora, [...] Read more.
Phosphoribosyl pyrophosphate synthetases (EC 2.7.6.1) are key enzymes in the biological synthesis of phosphoribosyl pyrophosphate and are involved in diverse developmental processes. In our previous study, the PRPS1 gene was discovered as a key disease-resistance candidate gene in yellow drum, Nibea albiflora, in response to the infection of Vibrio harveyi, through genome-wide association analysis. This study mainly focused on the characteristics and its roles in immune responses of the PRPS1 gene in yellow drum. In the present study, the NaPRPS1 gene was cloned from yellow drum, encoding a protein of 320 amino acids. Bioinformatic analysis showed that NaPRPS1 was highly conserved during evolution. Quantitative RT-PCR demonstrated that NaPRPS1 was highly expressed in the head-kidney and brain, and its transcription and translation were significantly activated by V. harveyi infection examined by RT-qPCR and immunohistochemistry analysis, respectively. Subcellular localization revealed that NaPRPS1 was localized in cytoplasm. In addition, semi-in vivo pull-down assay coupled with mass spectrometry identified myeloid differentiation factor 88 (MyD88) as an NaPRPS1-interacting patterner, and their interaction was further supported by reciprocal pull-down assay and co-immunoprecipitation. The inducible expression of MyD88 by V. harveyi suggested that the linker molecule MyD88 in innate immune response may play together with NaPRPS1 to coordinate the immune signaling in yellow drum in response to the pathogenic infection. We provide new insights into important functions of PRPS1, especially PRPS1 in the innate immunity of teleost fishes, which will benefit the development of marine fish aquaculture. Full article
(This article belongs to the Special Issue Cellular Signalling Pathways in Innate Immunity)
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