Single-Cell Analysis Reveals Characterization of Infiltrating T Cells in Moderately Differentiated Colorectal Cancer
ConclusionsWe characterized the T cell populations in the CRC tumor tissue and peripheral blood. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex
Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In or...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Review: Occurrence and Distribution of Galanin in the Physiological and Inflammatory States in the Mammalian Gastrointestinal Tract
Galanin (GAL) is a broad-spectrum peptide that was first identified 37 years ago. GAL, which acts through three specific receptor subtypes, is one of the most important molecules on an ever-growing list of neurotransmitters. Recent studies indicate that this peptide is commonly present in the gastrointestinal (GI) tract and GAL distribution can be seen in the enteric nervous system (ENS). The function of the GAL in the gastrointestinal tract is, inter alia, to regulate motility and secretion. It should be noted that the distribution of neuropeptides is largely dependent on the research model, as well as the part of the gas...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

RANK Signaling in the Differentiation and Regeneration of Thymic Epithelial Cells
Thymic epithelial cells (TECs) provide essential clues for the proliferation, survival, migration, and differentiation of thymocytes. Recent advances in mouse and human have revealed that TECs constitute a highly heterogeneous cell population with distinct functional properties. Importantly, TECs are sensitive to thymic damages engendered by myeloablative conditioning regimen used for bone marrow transplantation. These detrimental effects on TECs delay de novo T-cell production, which can increase the risk of morbidity and mortality in many patients. Alike that TECs guide the development of thymocytes, reciprocally thymocy...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

The Regulatory Role of High-Mobility Group Protein 1 in Sepsis-Related Immunity
High-mobility group box 1 (HMGB1), a prototypical damage-associated molecular pattern (DAMP) molecule, participates in multiple processes of various inflammatory diseases through binding to its corresponding receptors. In the early phase, sepsis is mainly characterized as a multi-bacterial-induced complex, excessive inflammatory response accompanied by the release of pro-inflammatory mediators, which subsequently develops into immune paralysis. A growing number of in vivo and in vitro investigations reveal that HMGB1 plays a pivotal role in the processes of inflammatory response and immunosuppression of sepsis. Therefore, ...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Protein Phosphatase PP1 Negatively Regulates IRF3 in Response to GCRV Infection in Grass Carp (Ctenopharyngodon idella)
In this study, the PPP1R3G homolog was identified in the grass carp (Ctenopharyngodon idella) and its role in defence against the GCRV infection was investigated. Phylogenetic analysis demonstrated that CiPPP1R3G clustered with homologues from other teleosts. Temporal expression analysis in vivo revealed that the expression level of CiPPP1R3G was significantly up-regulated in response to GCRV infection in grass carps, especially in the intestine and head-kidney. Cellular distribution analysis revealed that CiPPP1R3G was located in the nucleus and cytoplasm. Overexpression of CiPPP1R3G significantly negatively regulated the...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Podocyte Injury Through Interaction Between Tlr8 and Its Endogenous Ligand miR-21 in Obstructed and Its Collateral Kidney
In conclusion, the overexpression of Tlr8 may serve as a plausible mechanism underlying GL development in ON through podocyte injury. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling
In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Irradiated Tumor Fibroblasts Avoid Immune Recognition and Retain Immunosuppressive Functions Over Natural Killer Cells
This study was undertaken to determine whether ionizing radiation alters the CAF-mediated immunoregulatory effects on natural killer (NK) cells. CAFs were isolated from freshly resected non-small cell lung cancer tissues, while NK cells were prepared from peripheral blood of healthy donors. Functional assays to study NK cell immune activation included proliferation rates, expression of cell surface markers, secretion of immunomodulators, cytotoxic assays, as well as production of intracellular activation markers such as perforin and granzyme B. Our data show that CAFs inhibit NK cell activation by reducing their proliferat...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Does Antigen Glycosylation Impact the HIV-Specific T Cell Immunity?
It is largely unknown how post-translational protein modifications, including glycosylation, impacts recognition of self and non-self T cell epitopes presented by HLA molecules. Data in the literature indicate that O- and N-linked glycosylation can survive epitope processing and influence antigen presentation and T cell recognition. In this perspective, we hypothesize that glycosylation of viral proteins and processed epitopes contribute to the T cell response to HIV. Although there is some evidence for T cell responses to glycosylated epitopes (glyco-epitopes) during viral infections in the literature, this aspect has bee...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Immune Responses to Plasma-Derived Versus Recombinant FVIII Products
The most severe side effect of hemophilia treatment is the inhibitor development occurring in 30% of patients, during the earliest stages of treatment with factor (F)VIII concentrates. These catastrophic immune responses rapidly inactivate the infused FVIII, rendering the treatment ineffective. This complication is associated with a substantial morbidity and mortality. The risk factors involved in the onset of the inhibitors are both genetic and environmental. The source of FVIII products, i.e. plasma-derived or recombinant FVIII products, is considered one of the most relevant factors for inhibitor development. Numerous s...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Dim Light at Night Impairs Daily Variation of Circulating Immune Cells and Renal Immune Homeostasis
Dim light at night (dLAN) has become a pervasive part of the modern world, and growing evidence shows its association with increased health risks. Though this link is attributed to a disturbed circadian clock, the underlying mechanisms that can explain how circadian disruption from dLAN causes negative health effects remain unclear. Here, we exposed rats to a light–dark cycle (12:12 h) with low-intensity light at night (~2 lx) for 2 and 5 weeks and explored the steady-state pattern of circulating immune cells and renal immune-related markers, which are well controlled by the circadian clock. After 5 weeks, ...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Stereotactic Body Radiotherapy Is Effective in Modifying the Tumor Genome and Tumor Immune Microenvironment in Non-Small Cell Lung Cancer or Lung Metastatic Carcinoma
ConclusionSBRT improved the TCR repertoire diversity and PD-L1 expression in the TME and induced neo-mutation of genes in tumor cells but did not increase CD8+ T-cell infiltration and IFN expression in the tumor tissue within a week. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Delving Into the Origin of Destructive Inflammation in COVID-19: A Betrayal of Natural Host Defense Peptides?
In contrast to other pathogenic agents that directly destroy host cells and tissues, the lethal power of SARS-CoV-2 resides in the over-reactive immune response triggered by this virus. Based on numerous evidences indicating that the lipid composition of host membranes is dramatically affected by COVID-19, and in the fact that our endogenous antimicrobial peptides (AMPs) are sensitive to the membrane composition of pathogenic agents, we propose that such destructive immune response is due to the direct action of AMPs. In a scenario where most host cell membranes are dressed by a pathogenic lipid composition, AMPs can indis...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Chronic Hyperglycemia Drives Functional Impairment of Lymphocytes in Diabetic INSC94Y Transgenic Pigs
People with diabetes mellitus have an increased risk for infections, however, there is still a critical gap in precise knowledge about altered immune mechanisms in this disease. Since diabetic INSC94Y transgenic pigs exhibit elevated blood glucose and a stable diabetic phenotype soon after birth, they provide a favorable model to explore functional alterations of immune cells in an early stage of diabetes mellitus in vivo. Hence, we investigated peripheral blood mononuclear cells (PBMC) of these diabetic pigs compared to non-diabetic wild-type littermates. We found a 5-fold decreased proliferative response of T cells in IN...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Living in a Hostile World: Inflammation, New Drug Development, and Coronavirus
We present a brief history of the immune response and show that Metchnikoff’s theory of inflammation and phagocytotic defense was largely ignored in the 20th century. For decades, the immune response was believed to be triggered centrally, until Lafferty and Cunningham proposed the initiating signal came from the tissues. This shift opened the way for Janeway’s pattern recognition receptor theory, and Matzinger’s danger model. All models failed to appreciate that without inflammation, there can be no immune response. The situation changed in the 1990s when cytokine biology was rapidly advancing, and the i...
Source: Frontiers in Immunology - January 22, 2021 Category: Allergy & Immunology Source Type: research

Nonmicrobial Activation of TLRs Controls Intestinal Growth, Wound Repair, and Radioprotection
TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PGE2 production, which transactivates EGFR in LGR5+ crypt epithelial stem cells leading to increased proliferation. The expanded population of LGR5+ stem cells leads to crypt fission and lengtheni...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Lymphocyte-Specific Biomarkers Associated With Preterm Birth and Bronchopulmonary Dysplasia
Many premature babies who are born with neonatal respiratory distress syndrome (RDS) go on to develop Bronchopulmonary Dysplasia (BPD) and later Post-Prematurity Respiratory Disease (PRD) at one year corrected age, characterized by persistent or recurrent lower respiratory tract symptoms frequently related to inflammation and viral infection. Transcriptomic profiles were generated from sorted peripheral blood CD8+ T cells of preterm and full-term infants enrolled with consent in the NHLBI Prematurity and Respiratory Outcomes Program (PROP) at the University of Rochester and the University at Buffalo. We identified outcome-...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Distinct Immunophenotypes of T Cells in Bronchoalveolar Lavage Fluid From Leukemia Patients With Immune Checkpoint Inhibitors-Related Pulmonary Complications
Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated with immune checkpoint inhibitors (ICIs) are at risk of pneumonitis as well as pneumonia (combined henceforth as ICI-related pulmonary complications). Little is known about the cellular and molecular mechanisms underlying ICI-related pulmonary complications. We characterized lymphocytes from bronchoalveolar lavage (BAL) fluid and peripheral blood from seven AML/MDS patients with pulmonary symptoms after ICI-based therapy (ICI group) and four ICI-naïve AML/MDS patients with extracellular bacterial or fungal pneumonias (controls). BAL ...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

SIRP α Suppresses Response to Therapeutic Antibodies by Nurse Like Cells From Chronic Lymphocytic Leukemia Patients
In this study we examine whether the SIRPα axis regulates ADP responses to the anti-CD20 antibody, obinutuzumab, by NLCs. Using siRNA depletion strategies we show that SIRPα is a suppressor of ADP responses. Moreover, we show that this innate immune checkpoint contributes to the resistance phenotype in NLCs derived from CLL patients. Finally, we show that SIRPα suppression is mediated via the phosphatase, Shp1, which in turn suppresses SYK-dependent activation of ADP. Thus, we identify a druggable pathway that could be exploited to enhance sensitivity to existing therapeutic antibodies used in CLL. This i...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics
Sexual dimorphism refers to differences between biological sexes that extend beyond sexual characteristics. In humans, sexual dimorphism in the immune response has been well demonstrated, with females exhibiting lower infection rates than males for a variety of bacterial, viral, and parasitic pathogens. There is also a substantially increased incidence of autoimmune disease in females compared to males. Together, these trends indicate that females have a heightened immune reactogenicity to both self and non-self-molecular patterns. However, the molecular mechanisms driving the sexually dimorphic immune response are not ful...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

STING, the Endoplasmic Reticulum, and Mitochondria: Is Three a Crowd or a Conversation?
The anti-viral pattern recognition receptor STING and its partnering cytosolic DNA sensor cGAS have been increasingly recognized to respond to self DNA in multiple pathologic settings including cancer and autoimmune disease. Endogenous DNA sources that trigger STING include damaged nuclear DNA in micronuclei and mitochondrial DNA (mtDNA). STING resides in the endoplasmic reticulum (ER), and particularly in the ER-mitochondria associated membranes. This unique location renders STING well poised to respond to intracellular organelle stress. Whereas the pathways linking mtDNA and STING have been addressed recently, the mechan...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

The Role of Tenascin-C in Tissue Injury and Repair After Stroke
Stroke is still one of the most common causes for mortality and morbidity worldwide. Following acute stroke onset, biochemical and cellular changes induce further brain injury such as neuroinflammation, cell death, and blood-brain barrier disruption. Matricellular proteins are non-structural proteins induced by many stimuli and tissue damage including stroke induction, while its levels are generally low in a normal physiological condition in adult tissues. Currently, a matricellular protein tenascin-C (TNC) is considered to be an important inducer to promote neuroinflammatory cascades and the resultant pathology in stroke....
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

A Glance at the Use of Glucocorticoids in Rare Inflammatory and Autoimmune Diseases: Still an Indispensable Pharmacological Tool?
Since their discovery, glucocorticoids (GCs) have been used to treat almost all autoimmune and chronic inflammatory diseases, as well as allergies and some forms of malignancies, because of their immunosuppressive and anti-inflammatory effects. Although GCs provide only symptomatic relief and do not eliminate the cause of the pathology, in the majority of treatments, GCs frequently cannot be replaced by other classes of drugs. Consequently, long-term treatments cause adverse effects that may, in turn, lead to new pathologies that sometimes require the withdrawal of GC therapy. Therefore, thus far, researchers have focused ...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Variable Expression of Programmed Cell Death Protein 1-Ligand 1 in Kidneys Independent of Immune Checkpoint Inhibition
ConclusionOur study implicates that PD-L1 is frequently expressed in various renal pathologies independent of ICI therapy and could potentially be a pre-requisit for susceptibility to develop AKI and deleterious immune-related AIN. Because non-invasive detection of PD-L1+ cells in corresponding urine samples correlates with intrarenal PD-L1 positivity, it is attractive to speculate that further non-invasive detection of PD-L1+ cells may identify patients at risk for ICI-related AIN. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Understanding Early-Life Adaptive Immunity to Guide Interventions for Pediatric Health
Infants are capable of mounting adaptive immune responses, but their ability to develop long-lasting immunity is limited. Understanding the particularities of the neonatal adaptive immune system is therefore critical to guide the design of immune-based interventions, including vaccines, in early life. In this review, we present a thorough summary of T cell, B cell, and humoral immunity in early life and discuss infant adaptive immune responses to pathogens and vaccines. We focus on the differences between T and B cell responses in early life and adulthood, which hinder the generation of long-lasting adaptive immune respons...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Bactericidal Permeability Increasing Protein Deficiency Aggravates Acute Colitis in Mice by Increasing the Serum Levels of Lipopolysaccharide
ConclusionsWe successfully generated BPI KO mice. The BPI KO mice developed worse colitis than WT mice by increased colitis symptoms and colonic mucosal damage, elevated levels of serum LPS, and a disrupted microbiome. BPI could be a potential target for treatment of ulcerative colitis in humans. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Development of a Chimeric Vaccine Against Pseudomonas aeruginosa Based on the Th17-Stimulating Epitopes of PcrV and AmpC
Pulmonary infection caused by Pseudomonas aeruginosa (PA) has created an urgent need for an efficient vaccine, but the protection induced by current candidates is limited, partially because of the high variability of the PA genome. Antigens targeting pulmonary Th17 responses are able to provide antibody-independent and broad-spectrum protection; however, little information about Th17-stimulating antigens in PA is available. Herein, we identified two novel PA antigens that effectively induce Th17-dependent protection, namely, PcrV (PA1706) and AmpC (PA4110). Compared to intramuscular immunization, intranasal immunization en...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

A Dimerization Site at SCR-17/18 in Factor H Clarifies a New Mechanism for Complement Regulatory Control
Complement Factor H (CFH), with 20 short complement regulator (SCR) domains, regulates the alternative pathway of complement in part through the interaction of its C-terminal SCR-19 and SCR-20 domains with host cell-bound C3b and anionic oligosaccharides. In solution, CFH forms small amounts of oligomers, with one of its self-association sites being in the SCR-16/20 domains. In order to correlate CFH function with dimer formation and the occurrence of rare disease-associated variants in SCR-16/20, we identified the dimerization site in SCR-16/20. For this, we expressed, in Pichia pastoris, the five domains in SCR-16/20 and...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Research Status and Molecular Mechanism of the Traditional Chinese Medicine and Antitumor Therapy Combined Strategy Based on Tumor Microenvironment
This article summarizes the existing research on the molecular mechanism of TCM regulation of the TME and provides a theoretical basis for further screening of the predominant population. Moreover, it predicts the effects of the combination of TCM and antitumor therapy and proposes further developments in clinical practice to optimize the combined strategy. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Activation of the Nlrp3 Inflammasome Contributes to Shiga Toxin-Induced Hemolytic Uremic Syndrome in a Mouse Model
ConclusionNlrp3 inflammasome activation plays a vital role in the HUS development when mice are challenged by Stx2, and Oridonin is effective in preventing HUS. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

A Combination of Polybacterial MV140 and Candida albicans V132 as a Potential Novel Trained Immunity-Based Vaccine for Genitourinary Tract Infections
Recurrent urinary tract infections (RUTIs) and recurrent vulvovaginal candidiasis (RVVCs) represent major healthcare problems with high socio-economic impact worldwide. Antibiotic and antifungal prophylaxis remain the gold standard treatments for RUTIs and RVVCs, contributing to the massive rise of antimicrobial resistance, microbiota alterations and co-infections. Therefore, the development of novel vaccine strategies for these infections are sorely needed. The sublingual heat-inactivated polyvalent bacterial vaccine MV140 shows clinical efficacy for the prevention of RUTIs and promotes Th1/Th17 and IL-10 immune responses...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Initiation of Post-Primary Tuberculosis of the Lungs: Exploring the Secret Role of Bone Marrow Derived Stem Cells
Mycobacterium tuberculosis (Mtb), the causative organism of pulmonary tuberculosis (PTB) now infects more than half of the world population. The efficient transmission strategy of the pathogen includes first remaining dormant inside the infected host, next undergoing reactivation to cause post-primary tuberculosis of the lungs (PPTBL) and then transmit via aerosol to the community. In this review, we are exploring recent findings on the role of bone marrow (BM) stem cell niche in Mtb dormancy and reactivation that may underlie the mechanisms of PPTBL development. We suggest that pathogen’s interaction with the stem c...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Selective Host Cell Death by Staphylococcus aureus: A Strategy for Bacterial Persistence
Host cell death programs are fundamental processes that shape cellular homeostasis, embryonic development, and tissue regeneration. Death signaling and downstream host cell responses are not only critical to guide mammalian development, they often act as terminal responses to invading pathogens. Here, we briefly review and contrast how invading pathogens and specifically Staphylococcus aureus manipulate apoptotic, necroptotic, and pyroptotic cell death modes to establish infection. Rather than invading host cells, S. aureus subverts these cells to produce diffusible molecules that cause death of neighboring hematopoietic c...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Host Transcriptomic Response Following Administration of Rotavirus Vaccine in Infants ’ Mimics Wild Type Infection
DiscussionOur findings might shed further light in the understanding of RV infection, its functional link to intussusception causes, as well as guide development of antiviral treatments and safer and more effective vaccines. The nine-transcript signature may constitute a marker of vaccine protection and helps to differentiate vaccinated from naturally infected or susceptible children. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Dietary Indole-3-Carbinol Activates AhR in the Gut, Alters Th17-Microbe Interactions, and Exacerbates Insulitis in NOD Mice
The diet represents one environmental risk factor controlling the progression of type 1 diabetes (T1D) in genetically susceptible individuals. Consequently, understanding which specific nutritional components promote or prevent the development of disease could be used to make dietary recommendations in prediabetic individuals. In the current study, we hypothesized that the immunoregulatory phytochemcial, indole-3-carbinol (I3C) which is found in cruciferous vegetables, will regulate the progression of T1D in nonobese diabetic (NOD) mice. During digestion, I3C is metabolized into ligands for the aryl hydrocarbon receptor (A...
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

Integrated Analysis of circRNA-miRNA-mRNA Regulatory Networks in the Intestine of Sebastes schlegelii Following Edwardsiella tarda Challenge
This study revealed a landscape of RNAs in the intestine of S. schlegelii during E. tarda infection and provided clues for further study on the immune mechanisms and signaling networks based on the circRNA-miRNA-mRNA axis in S. schlegelii. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 21, 2021 Category: Allergy & Immunology Source Type: research

T Cells in Chronic Lymphocytic Leukemia: A Two-Edged Sword
Chronic lymphocytic leukemia (CLL) is a malignancy of mature, antigen-experienced B lymphocytes. Despite great progress recently achieved in the management of CLL, the disease remains incurable, underscoring the need for further investigation into the underlying pathophysiology. Microenvironmental crosstalk has an established role in CLL pathogenesis and progression. Indeed, the malignant CLL cells are strongly dependent on interactions with other immune and non-immune cell populations that shape a highly orchestrated network, the tumor microenvironment (TME). The composition of the TME, as well as the bidirectional intera...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Phosphoinositide 3-Kinase Signaling in the Tumor Microenvironment: What Do We Need to Consider When Treating Chronic Lymphocytic Leukemia With PI3K Inhibitors?
Phosphoinositide 3-kinases (PI3Ks) and their downstream proteins constitute a signaling pathway that is involved in both normal cell growth and malignant transformation of cells. Under physiological conditions, PI3K signaling regulates various cellular functions such as apoptosis, survival, proliferation, and growth, depending on the extracellular signals. A deterioration of these extracellular signals caused by mutational damage in oncogenes or growth factor receptors may result in hyperactivation of this signaling cascade, which is recognized as a hallmark of cancer. Although higher activation of PI3K pathway is common i...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

GBP1 Facilitates Indoleamine 2,3-Dioxygenase Extracellular Secretion to Promote the Malignant Progression of Lung Cancer
This study showed that IDO1 can bind to GBP1 and increase the extracellular secretion of IDO1 with the assistance of GBP1, thereby promoting the malignant proliferation and metastasis of lung cancer. In vitro study showed that the high expression levels of IDO1 and GBP1 in lung cancer cells promoted cell invasion and migration. In vivo study revealed that knock-down of IDO1 and GBP1 inhibited tumor growth and metastasis. In addition, Astragaloside IV reduces the extracellular secretion of IDO1 by blocking the interaction of IDO1 and GBP1, thereby reducing T cell exhaustion and inhibiting tumor progression. These results su...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia
The immunoproteasome, a special isoform of the 20S proteasome, is expressed when the cells receive an inflammatory signal. Immunoproteasome inhibition proved efficacy in the treatment of autoimmune diseases. However, the role of the immunoproteasome in the pathogenesis of immune thrombocytopenia (ITP) remains unknown. We found that the expression of the immunoproteasome catalytic subunit, large multifunctional protease 2 (LMP2), was significantly upregulated in peripheral blood mononuclear cells of active ITP patients compared to those of healthy controls. No significant differences in LMP7 expression were observed between...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

C-Reactive Protein-Based Strategy to Reduce Antibiotic Dosing for the Treatment of Pneumococcal Infection
C-reactive protein (CRP) is a component of innate immunity. The concentration of CRP in serum increases in microbial infections including Streptococcus pneumoniae infection. Employing a mouse model of pneumococcal infection, it has been shown that passively administered human wild-type CRP protects mice against infection, provided that CRP is injected into mice within two hours of administering pneumococci. Engineered CRP (E-CRP) molecules have been reported recently; unlike wild-type CRP, passively administered E-CRP protected mice against infection even when E-CRP was injected into mice after twelve hours of administerin...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Intestinal Stem Cells and Immune Cell Relationships: Potential Therapeutic Targets for Inflammatory Bowel Diseases
The mammalian intestine is the largest immune organ that contains the intestinal stem cells (ISC), differentiated epithelial cells (enterocytes, Paneth cells, goblet cells, tuft cells, etc.), and gut resident-immune cells (T cells, B cells, dendritic cells, innate lymphoid cell, etc.). Inflammatory bowel disease (IBD), a chronic inflammatory disease characterized by mucosa damage and inflammation, threatens the integrity of the intestine. The continuous renewal and repair of intestinal mucosal epithelium after injury depend on ISCs. Inflamed mucosa healing could be a new target for the improvement of cl...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia
The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and ...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Interferon Receptor Trafficking and Signaling: Journey to the Cross Roads
Like most plasma membrane proteins, type I interferon (IFN) receptor (IFNAR) traffics from the outer surface to the inner compartments of the cell. Long considered as a passive means to simply control subunits availability at the plasma membrane, an array of new evidence establishes IFNAR endocytosis as an active contributor to the regulation of signal transduction triggered by IFN binding to IFNAR. During its complex journey initiated at the plasma membrane, the internalized IFNAR complex, i.e. IFNAR1 and IFNAR2 subunits, will experience post-translational modifications and recruit specific effectors. These finely tu...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

B Cell –Activating Factor Promotes B Cell Survival in Ectopic Lymphoid Tissues in Nasal Polyps
Ectopic lymphoid tissues (eLTs) characterized by B cell aggregation contribute to the local immunoglobulin production in nasal polyps (NPs). B cell-activating factor (BAFF) is vital for B cell survival, proliferation, and maturation. The purpose of this study is to investigate whether BAFF is involved in the B cell survival and eLT formation in NPs. The mRNA and protein levels of BAFF in NP tissues with and without eLTs were detected by PCR and ELISA assay, respectively. The cellular sources of BAFF and active caspase-3-positive B cells in NPs were studied by immunofluorescence staining. B cells purified from NP tissues we...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Evaluation of Proteoforms of the Transmembrane Chemokines CXCL16 and CX3CL1, Their Receptors, and Their Processing Metalloproteinases ADAM10 and ADAM17 in Proliferative Diabetic Retinopathy
The transmembrane chemokine pathways CXCL16/CXCR6 and CX3CL1/CX3CR1 are strongly implicated in inflammation and angiogenesis. We investigated the involvement of these chemokine pathways and their processing metalloproteinases ADAM10 and ADAM17 in the pathophysiology of proliferative diabetic retinopathy (PDR). Vitreous samples from 32 PDR and 24 non-diabetic patients, epiretinal membranes from 18 patients with PDR, rat retinas, human retinal Müller glial cells and human retinal microvascular endothelial cells (HRMECs) were studied by enzyme-linked immunosorbent assay, immunohistochemistry and Western blot analysis. In...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Spatial Organization and Recruitment of Non-Specific T Cells May Limit T Cell-Macrophage Interactions Within Mycobacterium tuberculosis Granulomas
Tuberculosis (TB) is a worldwide health problem; successful interventions such as vaccines and treatment require a 2better understanding of the immune response to infection with Mycobacterium tuberculosis (Mtb). In many infectious diseases, pathogen-specific T cells that are recruited to infection sites are highly responsive and clear infection. Yet in the case of infection with Mtb, most individuals are unable to clear infection leading to either an asymptomatically controlled latent infection (the majority) or active disease (roughly 5%–10% of infections). The hallmark of Mtb infection is the recruitment of immune ...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis
ConclusionCurrent evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed. (Source: Frontiers in Immunology)
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research

Viral Infections in HSCT: Detection, Monitoring, Clinical Management, and Immunologic Implications
In spite of an increasing array of investigations, the relationships between viral infections and allogeneic hematopoietic stem cell transplantation (HSCT) are still controversial, and almost exclusively regard DNA viruses. Viral infections per se account for a considerable risk of morbidity and mortality among HSCT recipients, and available antiviral agents have proven to be of limited effectiveness. Therefore, an optimal management of viral infection represents a key point in HSCT strategies. On the other hand, viruses bear the potential of shaping immunologic recovery after HSCT, possibly interfering with control of the...
Source: Frontiers in Immunology - January 20, 2021 Category: Allergy & Immunology Source Type: research