Complex Involvement of Interleukin-26 in Bacterial Lung Infection
Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models ...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Chemical Stimulants and Stressors Impact the Outcome of Virus Infection and Immune Gene Expression in Honey Bees (Apis mellifera)
Western honey bees (Apis mellifera) are ecologically, agriculturally, and economically important plant pollinators. High average annual losses of honey bee colonies in the US have been partially attributed to agrochemical exposure and virus infections. To examine the potential negative synergistic impacts of agrochemical exposure and virus infection, as well as the potential promise of phytochemicals to ameliorate the impact of pathogenic infections on honey bees, we infected bees with a panel of viruses (i.e., Flock House virus, deformed wing virus, or Sindbis virus) and exposed to one of three chemical compounds. Specifi...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

GPR Expression in Intestinal Biopsies From SCT Patients Is Upregulated in GvHD and Is Suppressed by Broad-Spectrum Antibiotics
Microbiota can exert immunomodulatory effects by short-chain fatty acids (SCFA) in experimental models of graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-SCT). Therefore we aimed to analyze the expression of SCFAs sensing G-protein coupled receptor GPR109A and GPR43 by quantitative PCR in 338 gastrointestinal (GI) biopsies obtained from 199 adult patients undergoing allo-SCT and assessed the interaction of GPR with FOXP3 expression and regulatory T cell infiltrates. GPR expression was strongly upregulated in patients with stage II-IV GvHD (p=0.000 for GPR109A, p=0.01 for GPR4...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

CTNNB1 Alternation Is a Potential Biomarker for Immunotherapy Prognosis in Patients With Hepatocellular Carcinoma
ConclusionsIn this study, we found CTNNB1-MUT to be a potential biomarker for HCC immunotherapy patients, because it identified those patients are less likely to benefit from ICIs. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Highly Purified Alloantigen-Specific Tregs From Healthy and Chronic Kidney Disease Patients Can Be Long-Term Expanded, Maintaining a Suppressive Phenotype and Function in the Presence of Inflammatory Cytokines
The adoptive transfer of alloantigen-specific regulatory T cells (alloTregs) has been proposed as a therapeutic alternative in kidney transplant recipients to the use of lifelong immunosuppressive drugs that cause serious side effects. However, the clinical application of alloTregs has been limited due to their low frequency in peripheral blood and the scarce development of efficient protocols to ensure their purity, expansion, and stability. Here, we describe a new experimental protocol that allows the long-term expansion of highly purified allospecific natural Tregs (nTregs) from both healthy controls and chronic kidney ...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

UnAIDed Class Switching in Activated B-Cells Reveals Intrinsic Features of a Self-Cleaving IgH Locus
Activation-induced deaminase (AID) is the major actor of immunoglobulin (Ig) gene diversification in germinal center B-cells. From its first description, it was considered as mandatory for class switch recombination (CSR), and this discovery initiated a long quest for all of the AID-interacting factors controlling its activity. The mechanisms focusing AID-mediated DNA lesions to given target sequences remain incompletely understood with regards the detailed characterization of optimal substrates in which cytidine deamination will lead to double strand breaks (DSBs) and chromosomal cleavage. In an effort to reconsider wheth...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Immune Microenvironment and Response in Prostate Cancer Using Large Population Cohorts
This study used ssGSEA algorithm to explore expression levels of 53 immune terms in a combined PCa cohort (eight cohorts; 1,597 samples). The top 10 immune terms were selected based on the random forest analysis and used for immune-related risk score (IRS) calculation. Furthermore, we explored differences in clinical and genomic features between high and low IRS groups. An IRS signature based on the 10 immune terms showed high prediction potential for PCa prognosis. Patients in the high IRS group showed significantly higher percentage of immunotherapy response factors, implying that IRS is effective in predicting immunothe...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Human Cord Blood ILCs – Unusual Like My Career as a Scientist
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis
Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor characterized by rapid progression, early metastasis, high recurrence, and limited responsiveness to conventional therapies. The 5-year survival rate of PDAC is extremely low (
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Optimizing the Clinical Impact of CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia: Looking Back While Moving Forward
Chimeric antigen receptor T-cell (CAR-T) therapy has been successful in creating extraordinary clinical outcomes in the treatment of hematologic malignancies including relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). With several FDA approvals, CAR-T therapy is recognized as an alternative treatment option for particular patients with certain conditions of B-ALL, diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, or multiple myeloma. However, CAR-T therapy for B-ALL can be surrounded by challenges such as various adverse events including the life-threatening cytokine release ...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Plasma Gradient of Soluble Urokinase-Type Plasminogen Activator Receptor Is Linked to Pathogenic Plasma Proteome and Immune Transcriptome and Stratifies Outcomes in Severe COVID-19
We report here higher plasma abundance of suPAR, expressed by an abnormally expanded myeloid cell population, in severe COVID-19 patients with ARDS. The plasma suPAR level was found to be linked to a characteristic plasma proteome, associated with coagulation disorders and complement activation. Receiver operator characteristic curve analysis to predict mortality identified a cutoff value of suPAR at 1,996.809 pg/ml (odds ratio: 2.9286, 95% confidence interval 1.0427–8.2257). Lower-than-cutoff suPAR levels were associated with a differential expression of the immune transcriptome as well as favorable clinical outcome...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Slit2-Mediated Metabolic Reprogramming in Bone Marrow-Derived Macrophages Enhances Antitumor Immunity
Slit2 exerts antitumor effects in various cancers; however, the underlying mechanism, especially its role in regulating the immune, especially in the bone marrow niche, system is still unknown. Elucidating the behavior of macrophages in tumor progression can potentially improve immunotherapy. Using a spontaneous mammary tumor virus promoter-polyoma middle T antigen (PyMT) breast cancer mouse model, we observed that Slit2 increased the abundance of antitumor M1 macrophage in the bone marrow upon differentiation in vitro. Moreover, myeloablated PyMT mice injected with Slit2-treated bone marrow allografts showed a marked redu...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Multifunctional, TNF- α and IFN-γ-Secreting CD4 and CD8 T Cells and CD8High T Cells Are Associated With the Cure of Human Visceral Leishmaniasis
We described the evolution and participation of functional T cells during the treatment of patients with VL. Our results disclosed that the clinical improvement of patients is significantly associated with the participation of the CD4+ and CD8+ cytokine-secreting T cells. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Design and Immunological Validation of Macaca fascicularis Papillomavirus Type 3 Based Vaccine Candidates in Outbred Mice: Basis for Future Testing of a Therapeutic Papillomavirus Vaccine in NHPs
Persistent human papillomavirus (HPV) infections are causative for cervical neoplasia and carcinomas. Despite the availability of prophylactic vaccines, morbidity and mortality induced by HPV are still too high. Thus, an efficient therapy, such as a therapeutic vaccine, is urgently required. Herein, we describe the development and validation of Macaca fascicularis papillomavirus type 3 (MfPV3) antigens delivered via nucleic-acid and adenoviral vectors in outbred mouse models. Ten artificially fused polypeptides comprising early viral regulatory proteins were designed and optionally linked to the T cell adjuvant MHC-II-asso...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Maternal, Decidual, and Neonatal Lymphocyte Composition Is Affected in Pregnant Kidney Transplant Recipients
Pregnancy after renal transplantation is associated with an increased risk of complications. While a delicately balanced uterine immune system is essential for a successful pregnancy, little is known about the uterine immune environment of pregnant kidney transplant recipients. Moreover, children born to kidney transplant recipients are exposed in utero to immunosuppressive drugs, with possible consequences for neonatal outcomes. Here, we defined the effects of kidney transplantation on the immune cell composition during pregnancy with a cohort of kidney transplant recipients as well as healthy controls with uncomplicated ...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Dysregulated Inflammation During Obesity: Driving Disease Severity in Influenza Virus and SARS-CoV-2 Infections
Acute inflammation is a critical host defense response during viral infection. When dysregulated, inflammation drives immunopathology and tissue damage. Excessive, damaging inflammation is a hallmark of both pandemic influenza A virus (IAV) infections and Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Chronic, low-grade inflammation is also a feature of obesity. In recent years, obesity has been recognized as a growing pandemic with significant mortality and associated costs. Obesity is also an independent risk factor for increased disease severity and death during both IAV and SARS-CoV-2 infectio...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

The Use of Induced Pluripotent Stem Cells to Study the Effects of Adenosine Deaminase Deficiency on Human Neutrophil Development
In conclusion, the findings presented here demonstrate the important role of ADA in the development and function of neutrophils while clarifying the mechanisms responsible for the neutrophil abnormalities in ADA-deficient patients. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Type I Interferons Are Involved in the Intracellular Growth Control of Mycobacterium abscessus by Mediating NOD2-Induced Production of Nitric Oxide in Macrophages
Mycobacterium abscessus (MAB) is one of the rapidly growing, multidrug-resistant non-tuberculous mycobacteria (NTM) causing various diseases including pulmonary disorder. Although it has been known that type I interferons (IFNs) contribute to host defense against bacterial infections, the role of type I IFNs against MAB infection is still unclear. In the present study, we show that rIFN-β treatment reduced the intracellular growth of MAB in macrophages. Deficiency of IFN-α/β receptor (IFNAR) led to the reduction of nitric oxide (NO) production in MAB-infected macrophages. Consistently, rIFN-β treatment...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Immune Regulatory Cell Bias Following Alemtuzumab Treatment in Relapsing-Remitting Multiple Sclerosis
In this study (ClinicalTrials.gov ID# NCT03647722) we simultaneously analyzed the change in composition and function of both regulatory lymphocyte populations and distinct monocyte subsets in cross-sectional cohorts of MS patients prior to or 6, 12, 18, 24 or 36 months after their first course of alemtuzumab treatment. We found that the absolute number and percentage of cells with a regulatory B cell phenotype were significantly higher after treatment and were positivity correlated with regulatory T cells. In addition, B cells from treated patients secreted higher levels of IL-10 and BDNF, and inhibited the proliferation o...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

CMV Infection and CMV-Specific Immune Reconstitution Following Haploidentical Stem Cell Transplantation: An Update
Haploidentical stem cell transplantation (haploSCT) has advanced to a common procedure for treating patients with hematological malignancies and immunodeficiency diseases. However, cure is seriously hampered by cytomegalovirus (CMV) infections and delayed immune reconstitution for the majority of haploidentical transplant recipients compared to HLA-matched stem cell transplantation. Three major approaches, including in vivo T-cell depletion (TCD) using antithymocyte globulin for haploSCT (in vivo TCD-haploSCT), ex vivo TCD using CD34 + positive selection for haploSCT (ex vivo TCD-haploSCT), and T-cell replete...
Source: Frontiers in Immunology - October 28, 2021 Category: Allergy & Immunology Source Type: research

Corrigendum: To the Skin and Beyond: The Immune Response to African Trypanosomes as They Enter and Exit the Vertebrate Host
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma
High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up ...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Genome-Wide Profiling Reveals Alternative Polyadenylation of Innate Immune-Related mRNA in Patients With COVID-19
The coronavirus disease 2019 (COVID-19) pandemic has caused many deaths worldwide. To date, the mechanism of viral immune escape remains unclear, which is a great obstacle to developing effective clinical treatment. RNA processing mechanisms, including alternative polyadenylation (APA) and alternative splicing (AS), are crucial in the regulation of most human genes in many types of infectious diseases. Because the role of APA and AS in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown, we performed de novo identification of dynamic APA sites using a public dataset of human p...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Editorial: Nucleic Acid-Associated Inflammation
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Single Dose of a VSV-Based Vaccine Rapidly Protects Macaques From Marburg Virus Disease
Marburg virus (MARV) is a member of the filovirus family that causes hemorrhagic disease with high case fatality rates. MARV is on the priority list of the World Health Organization for countermeasure development highlighting its potential impact on global public health. We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) and previously demonstrated uniform protection of nonhuman primates (NHPs) with a single dose. Here, we investigated the fast-acting potential of this vaccine by challenging NHPs with MARV 14, 7 or 3 days after a single dose vaccination with VSV-MARV. ...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Generation of HLA Universal Megakaryocytes and Platelets by Genetic Engineering
Patelet transfusion refractoriness remains a relevant hurdle in the treatment of severe alloimmunized thrombocytopenic patients. Antibodies specific for the human leukocyte antigens (HLA) class I are considered the major immunological cause for PLT transfusion refractoriness. Due to the insufficient availability of HLA-matched PLTs, the development of new technologies is highly desirable to provide an adequate management of thrombocytopenia in immunized patients. Blood pharming is a promising strategy not only to generate an alternative to donor blood products, but it may offer the possibility to optimize the therapeutic e...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies
Over the past 20 years natural killer (NK) cell-based immunotherapies have emerged as a safe and effective treatment option for patients with relapsed or refractory leukemia. Unlike T cell-based therapies, NK cells harbor an innate capacity to eliminate malignant cells without prior sensitization and can be adoptively transferred between individuals without the need for extensive HLA matching. A wide variety of therapeutic NK cell sources are currently being investigated clinically, including allogeneic donor-derived NK cells, stem cell-derived NK cells and NK cell lines. However, it is becoming increasingly clear that not...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts
In conclusion, this study confirmed the influence of the LINC02549 and LRRC55 loci to determine the response to TNFi in RA patients and suggested a weak effect of the MAFB and CNTN5 loci that need to be further investigated. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Editorial: The State-of-Art in Immuno-Oncology, What to Do With Glioblastoma?
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Baseline Quantitative Hepatitis B Core Antibody Titer Is a Predictor for Hepatitis B Virus Infection Recurrence After Orthotopic Liver Transplantation
ConclusionLower pretransplantation qHBcAb is associated with HBV infection. The baseline concentration of qHBcAb is a promising predictor for the recurrence of HBV in patients undergoing liver transplantation and can be used to guide antiviral treatment for HBV infection. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors
Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 – 60 minute mixed mode aerobic exercises, comprising 10 – 30 minutes aerobic an...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Surfactant Proteins A/D –CD14 on Alveolar Macrophages Is a Common Pathway Associated With Phagocytosis of Nanomaterials and Cytokine Production
Alveolar macrophages are responsible for clearance of airborne dust and pathogens. How they recognize and phagocytose a variety of engineered nanomaterials (ENMs) with different properties is an important issue for safety assessment of ENMs. Surfactant-associated proteins, specifically existing in the pulmonary surfactant, are important opsonins for phagocytosis of airborne microorganisms. The purposes of the current study are to understand whether opsonization of ENMs by surfactant-associated proteins promotes phagocytosis of ENMs and cytokine production, and to determine whether a common pathway for phagocytosis of ENMs ...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

RASAL3 Is a Putative RasGAP Modulating Inflammatory Response by Neutrophils
As first responder cells in host defense, neutrophils must be carefully regulated to prevent collateral tissue injury. However, the intracellular events that titrate the neutrophil’s response to inflammatory stimuli remain poorly understood. As a molecular switch, Ras activity is tightly regulated by Ras GTPase activating proteins (RasGAP) to maintain cellular active-inactive states. Here, we show that RASAL3, a RasGAP, is highly expressed in neutrophils and that its expression is upregulated by exogenous stimuli in neutrophils. RASAL3 deficiency triggers augmented neutrophil responses and enhanced immune activation ...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Impact of Antibiotics and Proton Pump Inhibitors on Efficacy and Tolerance of Anti-PD-1 Immune Checkpoint Inhibitors
ConclusionsThis study reveals that ATB and/or PPI use can alter response to anti-PD1 ICI, and the prognosis of cancer patients. The microbiota mechanisms involved in the response to ICI should be investigated to optimize patient management. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

The Role of HDAC6 in Autophagy and NLRP3 Inflammasome
Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy an...
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

The Host Response to Viral Infections Reveals Common and Virus-Specific Signatures in the Peripheral Blood
In conclusion, our study will contribute to a better understanding of molecular mechanisms to viral infections in humans and the identification of biomarkers to distinguish different types of viral infections. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 27, 2021 Category: Allergy & Immunology Source Type: research

Mesenchymal Stromal Cells for the Treatment of Graft Versus Host Disease
Graft versus host disease (GvHD) is a life-threating complication of allogeneic hematopoietic stem cell transplantation, which is initially treated with high dose corticosteroids. Approximately 50% of acute GvHD cases are resistant to steroid treatment, and two-year mortality rates in those steroid-resistant patients exceed 80%. Chronic GvHD necessitates prolonged corticosteroid use, which is typically associated with limited efficacy and troublesome adverse effects. No agent has yet been established as an optimal second line therapy for either acute or chronic GvHD, but mesenchymal stromal cells (MSCs) have shown substant...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Human Complement C4B Allotypes and Deficiencies in Selected Cases With Autoimmune Diseases
Human complement C4 is one of the most diverse but heritable effectors for humoral immunity. To help understand the roles of C4 in the defense and pathogenesis of autoimmune and inflammatory diseases, we determined the bases of polymorphisms including the frequent genetic deficiency of C4A and/or C4B isotypes. We demonstrated the diversities of C4A and C4B proteins and their gene copy number variations (CNVs) in healthy subjects and patients with autoimmune disease, such as type 1 diabetes, systemic lupus erythematosus (SLE) and encephalitis. We identified subjects with (a) the fastest migrating C4B allotype, B7, or (b) a ...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

S100A9 Activates the Immunosuppressive Switch Through the PI3K/Akt Pathway to Maintain the Immune Suppression Function of Testicular Macrophages
Macrophages are functionally plastic and can thus play different roles in various microenvironments. Testis is an immune privileged organ, and testicular macrophages (TMs) show special immunosuppressive phenotype and low response to various inflammatory stimuli. However, the underlying mechanism to maintain the immunosuppressive function of TMs remains unclear. S100A9, a small molecular Ca2+ binding protein, is associated with the immunosuppressive function of macrophages. However, no related research is available about S100A9 in mouse testis. In the present study, we explored the role of S100A9 in TMs. We found that S100A...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Editorial: Modern Lifestyle and Health: How Changes in the Environment Impacts Immune Function and Physiology
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Following the Clues: Usefulness of Biomarkers of Neuroinflammation and Neurodegeneration in the Investigation of HTLV-1-Associated Myelopathy Progression
In conclusion, the slow progression of HAM/TSP abrogates the usefulness of biomarkers of neuronal injury for the disease prognosis. Thus, markers of inflammation provide stronger evidence for HAM/TSP progression, particularly the CSF/serum neopterin ratio, which may contribute to overcome differences between laboratory assays. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
Owing to broad and notable clinical anti-tumor activity, anti-programmed cell death-1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) antibodies have been indicated for almost all types of cancer, and form a part of the current standard of care. However, a large proportion of patients do not respond to anti-PD-1/PD-L1 therapy (primary resistance), and responders often develop progressive disease (acquired resistance). The mechanisms of resistance are complex and largely unknown; therefore, overcoming resistance remains clinically challenging, and data on reversing anti-PD-1 resistance are scarce. Herein, we report the c...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Pharmacological Activation Of Aldehyde Dehydrogenase 2 Protects Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction
Heatstroke (HS) can cause acute lung injury (ALI). Heat stress induces inflammation and apoptosis via reactive oxygen species (ROS) and endogenous reactive aldehydes. Endothelial dysfunction also plays a crucial role in HS-induced ALI. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that detoxifies aldehydes such as 4-hydroxy-2-nonenal (4-HNE) protein adducts. A single point mutation in ALDH2 at E487K (ALDH2*2) intrinsically lowers the activity of ALDH2. Alda-1, an ALDH2 activator, attenuates the formation of 4-HNE protein adducts and ROS in several disease models. We hypothesized that ALDH2 can protect against ...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Novel Allele Detection Tool Benchmark and Application With Antibody Repertoire Sequencing Dataset
Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Isolation and Characterization of Mouse Monoclonal Antibodies That Neutralize SARS-CoV-2 and Its Variants of Concern Alpha, Beta, Gamma and Delta by Binding Conformational Epitopes of Glycosylated RBD With High Potency
Antibodies targeting Receptor Binding Domain (RBD) of SARS-CoV-2 have been suggested to account for the majority of neutralizing activity in COVID-19 convalescent sera and several neutralizing antibodies (nAbs) have been isolated, characterized and proposed as emergency therapeutics in the form of monoclonal antibodies (mAbs). However, SARS-CoV-2 variants are rapidly spreading worldwide from the sites of initial identification. The variants of concern (VOC) B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.167.2 (Delta) showed mutations in the SARS-CoV-2 spike protein potentially able to cause escape from nAb responses ...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Case Report: The Carotid Body in COVID-19: Histopathological and Virological Analyses of an Autopsy Case Series
Various authors have hypothesized carotid body (CB) involvement in Coronavirus Disease 2019 (COVID-19), through direct invasion or indirect effects by systemic stimuli (‘cytokine storm’, angiotensin-converting enzyme [ACE]1/ACE2 imbalance). However, empirical evidence is limited or partial. Here, we present an integrated histopathological and virological analysis of CBs sampled at autopsy from four subjects (2 males and 2 females; age:>70 years old) who died of COVID-19. Histopathological, immunohistochemical and molecular investigation techniques were employed to characterize Severe Acute Respiratory Syndro...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Disruption of Glucocorticoid Action on CD11c+ Dendritic Cells Favors the Generation of CD4+ Regulatory T Cells and Improves Fetal Development in Mice
A wealth of innate and adaptive immune cells and hormones are involved in mounting tolerance towards the fetus, a key aspect of successful reproduction. We could recently show that the specific cross talk between the pregnancy hormone progesterone and dendritic cells (DCs) is significantly engaged in the generation of CD4+ FoxP3+ regulatory T (Treg) cells while a disruption led to placental alterations and intra-uterine growth restriction. Apart from progesterone, also glucocorticoids affect immune cell functions. However, their functional relevance in the context of pregnancy still needs clarification. We developed a mous...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Cross-Reactivity to Mutated Viral Immune Targets Can Influence CD8+ T Cell Functionality: An Alternative Viral Adaptation Strategy
Loss of T cell immunogenicity due to mutations in virally encoded epitopes is a well-described adaptation strategy to limit host anti-viral immunity. Another described, but less understood, adaptation strategy involves the selection of mutations within epitopes that retain immune recognition, suggesting a benefit for the virus despite continued immune pressure (termed non-classical adaptation). To understand this adaptation strategy, we utilized a single cell transcriptomic approach to identify features of the HIV-specific CD8+ T cell responses targeting non-adapted (NAE) and adapted (AE) forms of epitopes containing a non...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Immune-Related Genes to Construct a Novel Prognostic Model of Breast Cancer: A Chemosensitivity-Based Study
Chemotherapy combined with surgery is effective for patients with breast cancer (BC). However, chemoresistance restricts the effectiveness of BC treatment. Immune microenvironmental changes are of pivotal importance for chemotherapy responses. Thus, we sought to construct and validate an immune prognostic model based on chemosensitivity status in BC. Here, immune-related and chemosensitivity-related genes were obtained from GSE25055. Then, univariate analysis was employed to identify prognostic-related gene pairs from the intersection of the two parts of the genes, and modified least absolute shrinkage and selection operat...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research

Single-Cell Sequencing Reveals the Novel Role of Ezh2 in NK Cell Maturation and Function
Natural killer (NK) cells are lymphocytes primarily involved in innate immunity and exhibit important functional properties in antimicrobial and antitumoral responses. Our previous work indicated that the enhancer of zeste homolog 2 (Ezh2) is a negative regulator of early NK cell differentiation and function through trimethylation of histone H3 lysine 27 (H3K27me3). Here, we deleted Ezh2 from immature NK cells and downstream progeny to explore its role in NK cell maturation by single-cell RNA sequencing (scRNA-seq). We identified six distinct NK stages based on the transcriptional signature during NK cell maturation. Condi...
Source: Frontiers in Immunology - October 26, 2021 Category: Allergy & Immunology Source Type: research