scholarly journals Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Haibo Wu ◽  
Peiqi He ◽  
Yong Ren ◽  
Shiqi Xiao ◽  
Wei Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Myeloid Cells ◽  
Cell Types ◽  
High Dimensional ◽  
Viral Antigens ◽  
Multiple Organs ◽  
Immune Profiling ◽  
Insight Into

AbstractA complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

scholarly journals High-dimensional immune-profiling in cancer: implications for immunotherapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000363 ◽  
Author(s):  
Samuel Chuah ◽  
Valerie Chew
Keyword(s):  
Immune System ◽  
Immune Cell ◽  
Positive Impact ◽  
Cell Types ◽  
High Dimensional ◽  
Host Immune System ◽  
Cancer Therapies ◽  
Quality Of Data ◽  
New Information ◽  
Immune Profiling

Immunotherapy is a rapidly growing field for cancer treatment. In contrast to conventional cancer therapies, immunotherapeutic strategies focus on reactivating the immune system to mount an antitumor response. Despite the encouraging outcome in clinical trials, a large proportion of patients still do not respond to treatment and many experience different degrees of immune-related adverse events. Furthermore, it is now increasingly appreciated that even many conventional cancer therapies such as radiotherapy could have a positive impact on the host immune system for better clinical response. Hence, there is a need to better understand tumor immunity in order to design immunotherapeutic strategies, especially evidence-based combination therapies, for improved clinical outcomes. With this aim, cancer research turned its attention to profiling the immune contexture of either the tumor microenvironment (TME) or peripheral blood to uncover mechanisms and biomarkers which might aid in precision immunotherapeutics. Conventional technologies used for this purpose were limited by the depth and dimensionality of the data. Advances in newer techniques have, however, greatly improved the breadth and depth, as well as the quantity and quality of data that can be obtained. The result of these advances is a wealth of new information and insights on how the TME could be affected by various immune cell-types, and how this might in turn impact the clinical outcome of cancer patients . We highlight herein some of the high-dimensional technologies currently employed in immune profiling in cancer and summarize the insights and potential benefits they could bring in designing better cancer immunotherapies.

scholarly journals Exosomes in Severe Asthma: Update in Their Roles and Potential in Therapy

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Esmaeil Mortaz ◽  
Shamila D. Alipoor ◽  
Mohammad Varahram ◽  
Hamidreza Jamaati ◽  
Johan Garssen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Communication ◽  
Cell Types ◽  
Therapeutic Agents ◽  
Lipid Mediators ◽  
Inflammatory Microenvironment ◽  
Intracellular Communication ◽  
Underlying Mechanisms ◽  
Insight Into ◽  
Novel Therapeutic

Exosomes are nanosized vesicles and have recently been recognized as important players in cell-to-cell communication. Exosomes contain different mediators such as proteins, nucleic acids (DNA, mRNA, miRNAs, and other ncRNAs), and lipid mediators and can shuttle their exosomal content to both neighboring and distal cells. Exosomes are very effective in orchestrating immune responses in the airways and all cell types can contribute to the systemic exosome pool. Intracellular communication between the broad range of cell types within the lung is crucial in disease emphasizing the importance of exosomes. In asthma, exosomes affect the inflammatory microenvironment which ultimately determines the development or alleviation of the pathological symptoms. Recent studies in this area have provided insight into the underlying mechanisms of disease and led to interest in using exosomes as potential novel therapeutic agents.

scholarly journals The Level of Viral Infection of Antigen-Presenting Cells Correlates with the Level of Development of Theiler's Murine Encephalomyelitis Virus-Induced Demyelinating Disease

2014 ◽  
Vol 89 (3) ◽  
pp. 1867-1878 ◽  
Author(s):  
Young Hee Jin ◽  
Hyun Seok Kang ◽  
Wanqiu Hou ◽  
Liping Meng ◽  
Byung S. Kim
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Viral Infection ◽  
Demyelinating Disease ◽  
Antigen Presenting Cells ◽  
Cell Types ◽  
Innate Immune ◽  
Mhc Genes ◽  
Encephalomyelitis Virus ◽  
Antigen Presenting

ABSTRACTIntracerebral infection with Theiler's murine encephalomyelitis virus (TMEV) induces immune-mediated demyelinating disease in susceptible SJL/J mice but not in resistant C57BL/6 mice. Previous studies have indicated that the major histocompatibility complex (MHC) genes play the most prominent role in the development of TMEV-induced demyelinating disease. In this study, we used C57BL/6.S (B6.S) congenic mice, which carryH-2sMHC genes instead ofH-2bMHC genes in conjunction with the C57BL/6 (B6) background genes. Our data show that virus-infected B6.S mice are free from disease and have significantly lower viral loads than susceptible SJL mice, particularly in the spinal cord. A strong protective Th1-type T helper response with virtually no pathogenic Th17 response was detected in B6.S mice, in contrast to the reduced Th1- and robust Th17-type responses in SJL mice. Notably, lower levels of viral infectivity in B6.S antigen-presenting cells (APCs) correlated with the disease resistance and T-cell-type response.In vitrostudies using APCs from B6.S and SJL mice show that TLR2, -3, -4, and -7, but not TLR9, signaling can replace viral infection and augment the effect of viral infection in the differentiation of the pathogenic Th17 cell type. Taken together, these results strongly suggest that the viral replication levels in APCs critically affect the induction of protective versus pathogenic Th cell types via the signaling of pattern recognition receptors for innate immune responses. Our current findings further imply that the levels of viral infectivity/replication and TLR-mediated signaling play critical roles in the pathogenesis of chronic viral diseases.IMPORTANCEThis study indicates that innate immune cytokines produced in antigen-presenting cells stimulating the T cell immune responses during early viral infection play a critical role in determining the susceptibility of mice to the development of demyelinating disease. The level of innate immune cytokines reflects the level of initial viral infection in the antigen-presenting cells, and the level determines the development of T cell types, which are either protective or pathogenic. The level of initial viral infection to the cells is controlled by a gene or genes that are not associated with the major histocompatibility antigen complex genes. This finding has an important implication in controlling not only chronic viral infections but also infection-induced autoimmune-like diseases, which are closely associated with the pathogenic type of T cell responses.

Nanoparticle-plasma Membrane Interactions: Thermodynamics, Toxicity and Cellular Response

2020 ◽  
Vol 27 (20) ◽  
pp. 3330-3345
Author(s):  
Ana G. Rodríguez-Hernández ◽  
Rafael Vazquez-Duhalt ◽  
Alejandro Huerta-Saquero
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Cellular Response ◽  
Cellular Level ◽  
Membrane Interactions ◽  
Daily Lives ◽  
Cellular Physiology ◽  
Associated Proteins ◽  
First Contact ◽  
Insight Into

Nanomaterials have become part of our daily lives, particularly nanoparticles contained in food, water, cosmetics, additives and textiles. Nanoparticles interact with organisms at the cellular level. The cell membrane is the first protective barrier against the potential toxic effect of nanoparticles. This first contact, including the interaction between the cell membranes -and associated proteins- and the nanoparticles is critically reviewed here. Nanoparticles, depending on their toxicity, can cause cellular physiology alterations, such as a disruption in cell signaling or changes in gene expression and they can trigger immune responses and even apoptosis. Additionally, the fundamental thermodynamics behind the nanoparticle-membrane and nanoparticle-proteins-membrane interactions are discussed. The analysis is intended to increase our insight into the mechanisms involved in these interactions. Finally, consequences are reviewed and discussed.

scholarly journals In situ differentiation of iridophore crystallotypes underlies zebrafish stripe patterning

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dvir Gur ◽  
Emily J. Bain ◽  
Kory R. Johnson ◽  
Andy J. Aman ◽  
H. Amalia Pasoili ◽  
...  
Keyword(s):  
Skin Color ◽  
Cell Types ◽  
Color Pattern ◽  
Single Type ◽  
Sequencing Analysis ◽  
X Ray Diffraction ◽  
X Ray ◽  
Cryogenic Scanning Electron Microscopy ◽  
Different Cell Types

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.

scholarly journals Development of Fragility Curves for Piping and Slope Stability of River Levees

Water ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 738
Author(s):  
Nicola Rossi ◽  
Mario Bačić ◽  
Meho Saša Kovačević ◽  
Lovorka Librić
Keyword(s):  
Slope Stability ◽  
Fragility Curves ◽  
Safety Margin ◽  
Water Levels ◽  
Flood Event ◽  
Soil Parameters ◽  
Design Code ◽  
A Site ◽  
Insight Into

The design code Eurocode 7 relies on semi-probabilistic calculation procedures, through utilization of the soil parameters obtained by in situ and laboratory tests, or by the means of transformation models. To reach a prescribed safety margin, the inherent soil parameter variability is accounted for through the application of partial factors to either soil parameters directly or to the resistance. However, considering several sources of geotechnical uncertainty, including the inherent soil variability, measurement error and transformation uncertainty, full probabilistic analyses should be implemented to directly consider the site-specific variability. This paper presents the procedure of developing fragility curves for levee slope stability and piping as failure mechanisms that lead to larger breaches, where a direct influence of the flood event intensity on the probability of failure is calculated. A range of fragility curve sets is presented, considering the variability of levee material properties and varying durations of the flood event, thus providing crucial insight into the vulnerability of the levee exposed to rising water levels. The procedure is applied to the River Drava levee, a site which has shown a continuous trend of increased water levels in recent years.

scholarly journals NIR responsive tumor vaccine in situ for photothermal ablation and chemotherapy to trigger robust antitumor immune responses

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lirong Zhang ◽  
Jingjing Zhang ◽  
Lixia Xu ◽  
Zijian Zhuang ◽  
Jingjin Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Vaccine ◽  
Oxidative Polymerization ◽  
Delivery Mode ◽  
Tumor Treatment ◽  
One Pot ◽  
Photothermal Ablation ◽  
Prolonged Retention ◽  
The One

Abstract Background Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.

scholarly journals NF-κB in Cancer Immunity: Friend or Foe?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 355
Author(s):  
Guilhem Lalle ◽  
Julie Twardowski ◽  
Yenkel Grinberg-Bleyer
Keyword(s):  
Immune Responses ◽  
Therapeutic Potential ◽  
Cell Types ◽  
Transcriptional Activators ◽  
New Class ◽  
Complex Interactions ◽  
Cancer Immunity ◽  
Distinct Cell ◽  
Cancer Initiation ◽  
Cancer Outcome

The emergence of immunotherapies has definitely proven the tight relationship between malignant and immune cells, its impact on cancer outcome and its therapeutic potential. In this context, it is undoubtedly critical to decipher the transcriptional regulation of these complex interactions. Following early observations demonstrating the roles of NF-κB in cancer initiation and progression, a series of studies converge to establish NF-κB as a master regulator of immune responses to cancer. Importantly, NF-κB is a family of transcriptional activators and repressors that can act at different stages of cancer immunity. In this review, we provide an overview of the selective cell-intrinsic contributions of NF-κB to the distinct cell types that compose the tumor immune environment. We also propose a new view of NF-κB targeting drugs as a new class of immunotherapies for cancer.

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