Complex Stability and an Irrevertible Transition Reverted by Peptide and Fibroblasts in a Dynamic Model of Innate Immunity
We here apply a control analysis and various types of stability analysis to an in silico model of innate immunity that addresses the management of inflammation by a therapeutic peptide. Motivation is the observation, both in silico and in experiments, that this therapy is not robust. Our modeling results demonstrate how (1) the biological phenomena of acute and chronic modes of inflammation may reflect an inherently complex bistability with an irrevertible flip between the two modes, (2) the chronic mode of the model has stable, sometimes unique, steady states, while its acute-mode steady states are stable but not unique, ...
Source: Frontiers in Immunology - February 15, 2020 Category: Allergy & Immunology Source Type: research

Key Aspects of the Immunobiology of Haploidentical Hematopoietic Cell Transplantation
Hematopoietic stem cell transplantation from a haploidentical donor is increasingly used and has become a standard donor option for patients lacking an appropriately matched sibling or unrelated donor. Historically, prohibitive immunological barriers resulting from the high degree of HLA-mismatch included graft-vs.-host disease (GVHD) and graft failure. These were overcome with increasingly sophisticated strategies to manipulate the sensitive balance between donor and recipient immune cells. Three different approaches are currently in clinical use: (a) ex vivo T-cell depletion resulting in grafts with defined immune cell c...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Editorial: Immunoregulatory Mechanisms of Interferon
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

The Methyl-CpG-Binding Protein Mbd2 Regulates Susceptibility to Experimental Colitis via Control of CD11c+ Cells and Colonic Epithelium
In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2−/− mice displayed dramatically worse pathology than wild type controls during dextran sulfate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis sever...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Maternal-Fetal Interplay in Zika Virus Infection and Adverse Perinatal Outcomes
During pregnancy, the organization of complex tolerance mechanisms occurs to assure non-rejection of the semiallogeneic fetus. Pregnancy is a period of vulnerability to some viral infections, mainly during the first and second trimesters, that may cause congenital damage to the fetus. Recently, Zika virus (ZIKV) infection has gained great notoriety due to the occurrence of congenital ZIKV syndrome, characterized by fetal microcephaly, which results from the ability of ZIKV to infect placental cells and neural precursors in the fetus. Importantly, in addition to the congenital effects, studies have shown that perinatal ZIKV...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

The Irony of Humanization: Alemtuzumab, the First, But One of the Most Immunogenic, Humanized Monoclonal Antibodies
Alemtuzumab was designed to reduce the immunogenicity of the parent CD52-specific rat immunoglobulin. Although originally marketed for use in cancer (Mabcampath®), alemtuzumab is currently licensed and formulated for the treatment of relapsing multiple sclerosis (Lemtrada®). Perhaps due to its history as the first humanized antibody, the potential of immunogenicity of the molecule has been considered inconsequential, and anti-drug antibodies (ADA) responses were similarly reported as being clinically insignificant. Nonetheless, despite humanization and depletion of peripheral T and B cells, alemtuzumab probably gen...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

IL-17A Modulates Peritoneal Macrophage Recruitment and M2 Polarization in Endometriosis
In this study, we investigated whether IL-17A could induce macrophage recruitment and M2 polarization, while promoting endometriotic lesion growth through enhanced vascularization. By utilizing a co-culture of macrophage-like THP-1 cells with an endometriotic epithelial cell line, our in vitro results suggest that IL-17A indirectly induces M2 markers CCL17 and CD206 by interacting with endometriotic epithelial cells. Further, in a syngeneic mouse model of endometriosis, IL-17A treatment increased macrophages in the peritoneum, which were also M2 in phenotype. However, IL-17A treatment did not augment proliferation or vascu...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

The Imbalance of Circulating Follicular Helper T Cells and Follicular Regulatory T Cells Is Associated With Disease Activity in Patients With Ulcerative Colitis
Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colon and rectum, in which the abnormality of B cells is involved in both its pathogenesis and progression. Follicular helper T cells (TFH) play an important role in assisting the immune function of human B cells in germinal centers, and follicular regulatory T cells (TFR) have the function of inhibiting TFH and germinal center B cell responses. The significance of circulating TFH and TFR in ulcerative colitis (UC) remains unclear. We analyzed peripheral blood of active and stable remission UC patients and found that circulating TFR was significa...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

A Tissue-Specific Rhythmic Recruitment Pattern of Leukocyte Subsets
The circulating of leukocytes in the vasculature to reach various organs is a crucial step that allows them to perform their function. With a sequence of interaction with the endothelial cells, the leukocytes emigrate from the circulation either by firm attachment to vascular beds or by trafficking into the tissues. Recent findings reveal that the leukocyte recruitment shows time as well as tissue specificity depending on the cell type and homing location. This spatiotemporal distribution of leukocyte subsets is driven by the circadian expression of pro-migratory molecules expressed on the leukocytes and the endothelium. B...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Fc Receptor-Like 6 (FCRL6) Discloses Progenitor B Cell Heterogeneity That Correlates With Pre-BCR Dependent and Independent Pathways of Natural Antibody Selection
B-1a cells produce “natural” antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, and differentiation properties conducive for natural Ab generation. Compared to FCRL6− pro B cells, the repressed mitotic, DNA damage repair, and signaling activity of FCRL6+ progenitors, yielded VH repertoires with biased distal Ighv segment accessibility, constraine...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Activation of the Kynurenine Pathway in Human Malignancies Can Be Suppressed by the Cyclin-Dependent Kinase Inhibitor Dinaciclib
In this study, glioblastoma multiforme (GBM) as well as head and neck squamous cell carcinomas (HNSCC) were examined because of their different mechanisms of spontaneous and treatment-induced immune escape. Effects on gene expression and protein levels were examined. Accompanying assessment of TRP metabolites from treated GBM cell culture supernatants was conducted. Our results show a heterogeneous and inversely correlated expression profile of TRP-metabolizing genes among GBM and HNSCC cells, with low, but inducible IDO1 expression upon IFNγ treatment. TDO2 expression was higher in GBM cells, while genes encoding ky...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Targeting Extracellular Vesicles to the Arthritic Joint Using a Damaged Cartilage-Specific Antibody
The targeted delivery of therapies to diseased tissues offers a safe opportunity to achieve optimal efficacy while limiting systemic exposure. These considerations apply to many disease indications but are especially relevant for rheumatoid arthritis (RA), as RA is a systemic autoimmune disease which affects multiple joints. We have identified an antibody that is specific to damaged arthritic cartilage (anti-ROS-CII) that can be used to deliver treatments specifically to arthritic joints, yielding augmented efficacy in experimental arthritis. In the current study, we demonstrate that scaffolds enriched with bioactive paylo...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Recombinant DnaK Orally Administered Protects Axenic European Sea Bass Against Vibriosis
This study was conducted to evaluate immunostimulation by Escherichia coli HSP70 (DnaK) in axenic European sea bass larvae in order to protect the larvae against vibriosis. DnaK stimulates the immune response in crustaceans and juvenile fish against bacterial infections. The use of axenic fish larvae allows to study immunostimulation in the absence of an interfering microbial community. At 7 days post-hatching, larvae received a single dose of alginate encapsulated recombinant DnaK. Two non-treated control groups in which animals either received empty alginate microparticles (C1) or no alginante microparticles (C2 and C3) ...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Immunogenicity of Potential CD4+ and CD8+ T Cell Epitopes Derived From the Proteome of Leishmania braziliensis
Conclusions: The peptide epitopes can differentially stimulate cells from SC, AD, and PT individuals, leading to distinct immune responses. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Engineered Nanomaterials and Type I Allergic Hypersensitivity Reactions
Type I allergic hypersensitivity disorders (atopy) including asthma, atopic dermatitis, allergic rhinitis, and food allergy are on the rise in developed and developing countries. Engineered nanomaterials (ENMs) span a large spectrum of material compositions including carbonic, metals, polymers, lipid-based, proteins, and peptides and are being utilized in a wide range of industries including healthcare and pharmaceuticals, electronics, construction, and food industry, and yet, regulations for the use of ENMs in consumer products are largely lacking. Prior evidence has demonstrated the potential of ENMs to induce and/or agg...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Autoantibody Specificities in Myasthenia Gravis; Implications for Improved Diagnostics and Therapeutics
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatiguability of skeletal muscles. It is an antibody-mediated disease, caused by autoantibodies targeting neuromuscular junction proteins. In the majority of patients (~85%) antibodies against the muscle acetylcholine receptor (AChR) are detected, while in 6% antibodies against the muscle-specific kinase (MuSK) are detected. In ~10% of MG patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG), making the improvement of methods for the detection of known autoantibodies or...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Autophagy Protects Against Developing Increased Lung Permeability and Hypoxemia by Down Regulating Inflammasome Activity and IL-1 β in LPS Plus Mechanical Ventilation-Induced Acute Lung Injury
Targeting inflammasome activation to modulate interleukin (IL)-1β is a promising treatment strategy against acute respiratory distress syndrome and ventilator-induced lung injury (VILI). Autophagy is a key regulator of inflammasome activation in macrophages. Here, we investigated the role of autophagy in the development of acute lung injury (ALI) induced by lipopolysaccharide (LPS) and mechanical ventilation (MV). Two hours before starting MV, 0.2 mg/kg LPS was administered to mice intratracheally. Mice were then placed on high-volume MV (30 ml/kg with 3 cmH2O positive end-expiratory pressure for 2.5 h without additio...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

c-MAF, a Swiss Army Knife for Tolerance in Lymphocytes
Beyond its well-admitted role in development and organogenesis, it is now clear that the transcription factor c-Maf has owned its place in the realm of immune-related transcription factors. Formerly introduced solely as a Th2 transcription factor, the role attributed to c-Maf has gradually broadened over the years and has extended to most, if not all, known immune cell types. The influence of c-Maf is particularly prominent among T cell subsets, where c-Maf regulates the differentiation as well as the function of multiple subsets of CD4 and CD8 T cells, lending it a crucial position in adaptive immunity and anti-tumoral re...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

CD1b Tetramers Broadly Detect T Cells That Correlate With Mycobacterial Exposure but Not Tuberculosis Disease State
The non-polymorphic nature of CD1 proteins creates a situation in which T cells with invariant T cell receptors (TCRs), like CD1d-specific NKT cells, are present in all humans. CD1b is an abundant protein on human dendritic cells that presents M. tuberculosis (Mtb) lipid antigens to T cells. Analysis of T cell clones suggested that semi-invariant TCRs exist in the CD1b system, but their prevalence in humans is not known. Here we used CD1b tetramers loaded with mycolic acid or glucose monomycolate to study polyclonal T cells from 150 Peruvian subjects. We found that CD1b tetramers loaded with mycolic acid or glucose monomyc...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Malnutrition Decreases Antibody Secreting Cell Numbers Induced by an Oral Attenuated Human Rotavirus Vaccine in a Human Infant Fecal Microbiota Transplanted Gnotobiotic Pig Model
Human rotavirus (HRV) is a leading cause of morbidity and mortality in children, especially in developing countries. Malnutrition is prevalent in these countries, which may contribute to the decreased oral vaccine efficacy, posing a concern for global health. Neonatal gnotobiotic (Gn) pigs closely resemble human infants in their anatomy, physiology, and outbred status and are a unique model to investigate malnutrition, oral live attenuated HRV (AttHRV) vaccination, and subsequent virulent HRV (VirHRV) challenge. We evaluated the impact of malnutrition on AttHRV vaccine efficacy and B cell immune responses in neonatal germf...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate Treated, Show More DNA Methylation Differences in CD4+ Memory Than in CD4+ Na ïve T Cells
Conclusion: Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Neoantigens in Hematologic Malignancies
T cell cancer neoantigens are created from peptides derived from cancer-specific aberrant proteins, such as mutated and fusion proteins, presented in complex with human leukocyte antigens on the cancer cell surface. Because expression of the aberrant target protein is exclusive to malignant cells, immunotherapy directed against neoantigens should avoid “on-target, off-tumor” toxicity. The efficacy of neoantigen vaccines in melanoma and glioblastoma and of adoptive transfer of neoantigen-specific T cells in epithelial tumors indicates that neoantigens are valid therapeutic targets. Improvements in sequencing tec...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Streptococcal Extracellular Membrane Vesicles Are Rapidly Internalized by Immune Cells and Alter Their Cytokine Release
Extracellular vesicles are membranous structures shed by almost every living cell. Bacterial gram-negative outer membrane vesicles (OMVs) and gram-positive membrane vesicles (MVs) play important roles in adaptation to the surrounding environment, cellular components' exchange, transfer of antigens and virulence factors, and infection propagation. Streptococcus pneumoniae is considered one of the priority pathogens, with a global health impact due to the increase in infection burden and growing antibiotic resistance. We isolated MVs produced from the S. pneumoniae reference strain (R6) and purified them via size exclusion c...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

NS5 Conservative Site Is Required for Zika Virus to Restrict the RIG-I Signaling
During host–virus co-evolution, cells develop innate immune systems to inhibit virus invasion, while viruses employ strategies to suppress immune responses and maintain infection. Here, we reveal that Zika virus (ZIKV), a re-emerging arbovirus causing public concerns and devastating complications, restricts host immune responses through a distinct mechanism. ZIKV nonstructural protein 5 (NS5) interacts with the host retinoic acid-inducible gene I (RIG-I), an essential signaling molecule for defending pathogen infections. NS5 subsequently represses K63-linked polyubiquitination of RIG-I, attenuates the phosphorylation...
Source: Frontiers in Immunology - February 14, 2020 Category: Allergy & Immunology Source Type: research

Microbial Regulation of Enteric Eosinophils and Its Impact on Tissue Remodeling and Th2 Immunity
Eosinophils have emerged as multifaceted cells that contribute to tissue homeostasis. However, the impact of the microbiota on their frequency and function at mucosal sites remains unclear. Here, we investigated the role of the microbiota in the regulation of enteric eosinophils. We found that small intestinal (SI) eosinophilia was significantly greater in germ-free (GF) mice compared to specific pathogen free (SPF) controls. This was associated with changes in the production of enteric signals that regulate eosinophil attraction and survival, and was fully reversed by complex colonization. Additionally, SI eosinophils of ...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Influenza A Virus Pre-Infection Exacerbates Pseudomonas aeruginosa-Mediated Lung Damage Through Increased MMP-9 Expression, Decreased Elafin Production and Tissue Resilience
Individuals with impaired immune responses, such as ventilated and cystic fibrosis patients are often infected with Pseudomonas aeruginosa (P.a) bacteria, and a co-infection with the Influenza virus (IAV) is often present. It has been known for many years that infection with IAV predisposes the host to secondary bacterial infections (such as Streptococcus pneumoniae or Staphylococcus aureus), and there is an abundance of mechanistic studies, including those studying the role of desensitization of TLR signaling, type I IFN- mediated impairment of neutrophil chemokines and antimicrobial production, attenuation of IL1β p...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Serafino Zappacosta: An Enlightened Mentor and Educator
With this article, the authors aim to honor the memory of Serafino Zappacosta, who had been their mentor during the early years of their career in science. The authors discuss how the combination of Serafino Zappacosta's extraordinary commitment to teaching and passion for science created a fostering educational environment that led to the creation of the “Ruggero Ceppellini Advanced School of Immunology.” The review also illustrates how the research on the MHC and the inspirational scientific context in the Zappacosta's laboratory influenced the authors' early scientific interests, and subsequent professional ...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Hepatocyte-Specific Deletion of AMPK α1 Results in Worse Outcomes in Mice Subjected to Sepsis in a Sex-Specific Manner
In conclusion, our study demonstrates that AMPKα1 is a crucial hepatoprotective enzyme during sepsis. Furthermore, our results suggest that AMPK-dependent liver metabolic functions may influence the susceptibility to multiple organ injury in a sex-dependent manner. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Tumor-Specific T Cell Activation in Malignant Brain Tumors
Due to their delicate locations as well as aggressive and infiltrative behavior, malignant brain tumors remain a therapeutic challenge. Harnessing the efficacy and specificity of the T-cell response to counteract malignant brain tumor progression and recurrence, represents an attractive treatment option. With the tremendous advances in the current era of immunotherapy, ongoing studies aim to determine the best treatment strategies for mounting a tumor-specific immune response against malignant brain tumors. However, immunosuppression in the local tumor environment, molecular and cellular heterogeneity as well as a lack of ...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

NK Cell-Based Immune Checkpoint Inhibition
Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Adaptive Immunity: New Aspects of Pathogenesis Underlying Neurodegeneration in Glaucoma and Optic Neuropathy
Glaucoma is a globally unmet medical challenge and the most prevalent neurodegenerative disease, which permanently damages the optic nerve and retinal ganglion cells (RGCs), leading to irreversible blindness. Present therapies target solely at lowering intraocular ocular pressure (IOP), a major risk factor of the disease; however, elevated IOP is neither necessary nor sufficient to cause glaucoma. Glaucomatous RGC and nerve fiber loss also occur in individuals with normal IOP. Recent studies have provided evidence indicating a link between elevated IOP and T cell-mediated autoimmune responses, particularly that are specifi...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Transcriptomic Features of T Cell-Barren Tumors Are Conserved Across Diverse Tumor Types
Conclusions: This study presents the first evidence that solid tumors of diverse anatomical origin acquire conserved transcriptional alterations that may be operative in the T cell-cold state. Our findings demonstrate the potential clinical utility of CD8-Low tumor-associated genes for predicting patient immunotherapy outcomes and point to novel mechanisms with potential for broad therapeutic exploitation. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

In utero Exposure to Maternal Chronic Inflammation Transfers a Pro-Inflammatory Profile to Generation F2 via Sex-Specific Mechanisms
Generational transfer of maladaptations in offspring have been reported to persist for multiple generations in conditions of chronic inflammation, metabolic and psychological stress. Thus, the current study aimed to expand our understanding of the nature, potential sex specificity, and transgenerational plasticity of inflammatory maladaptations resulting from maternal chronic inflammation. Briefly, F1 and F2 generations of offspring from C57/BL/6 dams exposed to a modified maternal periconception systemic inflammation (MSPI) protocol were profiled in terms of leukocyte and splenocyte counts and cytokine responses, as well ...
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Corrigendum: Critical Role of Alternative M2 Skewing in miR-155 Deletion-Mediated Protection of Colitis
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 13, 2020 Category: Allergy & Immunology Source Type: research

Corrigendum: Subcutaneous Immunization of Dogs With Bordetella bronchiseptica Bacterial Ghost Vaccine
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 12, 2020 Category: Allergy & Immunology Source Type: research

Bacillus S-Layer-Mediated Innate Interactions During Endophthalmitis
We reported that the absence of Bacillus surface layer protein (SLP) significantly blunted endophthalmitis severity. Here, we further investigated SLP in the context of Bacillus-retinal cell interactions and innate immune pathways to explore the mechanisms by which SLP contributes to intraocular inflammation. We compared phenotypes of Wild-type (WT) and SLP deficient (ΔslpA) Bacillus thuringiensis by analyzing bacterial adherence to and phagocytosis by human retinal Muller cells and phagocytosis by mouse neutrophils. Innate immune receptor activation by the Bacillus envelope and purified SLP was analyzed using TLR2/4...
Source: Frontiers in Immunology - February 12, 2020 Category: Allergy & Immunology Source Type: research

Interleukin-27 Enforces Regulatory T Cell Functions to Prevent Graft-versus-Host Disease
Graft-versus-host disease (GvHD) remains a significant complication of allogeneic hematopoietic cell transplantation (HCT), associated with significant morbidity and mortality. GvHD is characterized by dysregulated immune responses and resulting tissue damage of target organs. Recent investigations have focused on Foxp3+ regulatory T cells (Tregs) as a therapeutic tool, based on its regulatory functions in GvHD pathogenesis and their instrumental role in mitigating GvHD severity while preserving graft-versus-leukemia (GvL) activity. There are several challenges to its clinical application, including their paucity, impaired...
Source: Frontiers in Immunology - February 12, 2020 Category: Allergy & Immunology Source Type: research

Placental Protein 13 (Galectin-13) Polarizes Neutrophils Toward an Immune Regulatory Phenotype
Termed as galectin-13, placental protein 13 (PP13) is exclusively expressed in the placenta of anthropoid primates. Research on PP13 in normal and pathologic pregnancies show alteration of PP13 concentrations in pregnancy affected by preeclampsia or gestational diabetes. Galectins are also described as potent immunomodulators, and PP13 regulates T cell function in the placenta. Therefore, this study aims to investigate the effects of PP13 on neutrophils; a cell type often ignored in pregnancy, but present in the uterus and placenta from the early stages of pregnancy. Since neutrophil function is dysregulated during patholo...
Source: Frontiers in Immunology - February 12, 2020 Category: Allergy & Immunology Source Type: research

The Immunomodulatory Properties of the Human Amnion-Derived Mesenchymal Stromal/Stem Cells Are Induced by INF- γ Produced by Activated Lymphomonocytes and Are Mediated by Cell-To-Cell Contact and Soluble Factors
In this study, we aimed to establish the potential role of human amnion-derived MSCs (hAMSCs), in immunomodulation. We found that the immunosuppressive properties of hAMSCs are not constitutive, but require “supportive signals” capable of promoting these properties. Indeed, we observed that hAMSCs alone are not able to produce an adequate amount of soluble immunomodulatory factors. Here, we studied, in depth, the strong immunomodulatory licensing signal deriving from the direct interaction between hAMSCs and stimulated peripheral blood mononuclear cells. We found that the immunomodulatory effect of hAMSCs also ...
Source: Frontiers in Immunology - February 12, 2020 Category: Allergy & Immunology Source Type: research

Uncovering Low-Level Maternal Gonosomal Mosaicism in X-Linked Agammaglobulinemia: Implications for Genetic Counseling
This study underscores the importance of accurately establishing the parents' status on detection of an apparently de novo mutation in a patient, as inadvertent low-level mosaicism may lead to misinterpretation of the risk of recurrence, vital for genetic counseling. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 12, 2020 Category: Allergy & Immunology Source Type: research

Pregnancy Gestation Impacts on HIV-1-Specific Granzyme B Response and Central Memory CD4 T Cells
In this study we aimed to define pregnancy and gestation related changes to HIV-1-specific responses and T-cell phenotype in ART treated HIV-1 positive pregnant women. Eleven non-pregnant and 24 pregnant HIV-1 positive women were recruited, peripheral blood samples taken, fresh cells isolated, and compared using ELISpot assays and flow cytometry analysis. Clinical data were collected as part of standard care, and non-parametric statistics used. Alterations in induced IFNγ, IL-2, IL-10, and granzyme B secretion by peripheral blood mononuclear cells in response to HIV-1 Gag and Nef peptide pools and changes in T-cell s...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

Editorial: The Role of Complement in Tumors
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens
Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research have elucidated host mechanisms that contribute to the bacterial clearance where an indispensable role of immune cells has been established. However, the role of respiratory epithelial cells in bacterial clearance has garnered limited attention due to their weak inflammatory or phagocytic ability compared to immune cells such as macrophages and neutrophils. These studies often underappreciate the fact that epithelial cells are the most abundant cells in the...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

Serotonin: A Potent Immune Cell Modulator in Autoimmune Diseases
Serotonin, also known as 5-hydroxytryptamine (5-HT) is a signaling mediator that regulates emotion, behavior, and cognition. Previous studies have focused more on the roles of 5-HT in the central nervous system (CNS). However, 5-HT also shares a strong relationship with the pathological cases of tumor, inflammation, and pathogen infection. 5-HT participates in tumor cell migration, metastatic dissemination, and angiogenesis. In addition, 5-HT affects immune regulation via different 5-HT receptors (5-HTRs) expressed immune cells, including both innate and adaptive immune system. Recently, drugs targeting at 5-HT signaling w...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

Editorial: Innate Immunity Programming and Memory in Resolving and Non-Resolving Inflammation
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

Commentary: Triggering Receptor Expressed on Myeloid Cells-1 Inhibitor Targeted to Endothelium Decreases Cell Activation
(Source: Frontiers in Immunology)
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

T Cell Responses to Mycobacterial Glycolipids: On the Spectrum of “Innateness”
Diseases due to mycobacteria, including tuberculosis, leprosy, and Buruli ulcer, rank among the top causes of death and disability worldwide. Animal studies have revealed the importance of T cells in controlling these infections. However, the specific antigens recognized by T cells that confer protective immunity and their associated functions remain to be definitively established. T cells that respond to mycobacterial peptide antigens exhibit classical features of adaptive immunity and have been well-studied in humans and animal models. Recently, innate-like T cells that recognize lipid and metabolite antigens have also b...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

The Proteolytic Cleavage of Therapeutic Monoclonal Antibody Hinge Region: More Than a Matter of Subclass
The hinge region of immunoglobulin G (IgG) is involved in C1q and FcγRIIIA-expressing natural killer (NK) cell recruitment. Both heavy chains (HCs) of the hinge region can be cleaved sequentially by several proteases of the tumor/inflammatory/infectious microenvironment, including matrix metalloproteinase 12 (MMP12), or immunoglobulin-degrading enzyme from Streptococcus pyogenes (IdeS), impairing Fc-mediated functions. The cleavage of therapeutic monoclonal antibodies (TmAbs), which are based on a human IgG1, IgG2 or IgG4 structure, has been poorly investigated, although it may represent an escape mechanism to these ...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

Insights Into Lung Cancer Immune-Based Biology, Prevention, and Treatment
Lung cancer is the number one cause of cancer-related deaths. The malignancy is characterized by dismal prognosis and poor clinical outcome mostly due to advanced-stage at diagnosis, thereby inflicting a heavy burden on public health worldwide. Recent breakthroughs in immunotherapy have greatly benefited a subset of lung cancer patients, and more importantly, they are undauntedly bringing forth a paradigm shift in the drugs approved for cancer treatment, by introducing “tumor-type agnostic therapies”. Yet, and to fulfill immunotherapy's potential of personalized cancer treatment, demarcating the immune and geno...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy
The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both the classical and alternative pathways in vitreous humor and serum samples from proliferative DR (PDR) patients and controls. Fur...
Source: Frontiers in Immunology - February 11, 2020 Category: Allergy & Immunology Source Type: research