Deep Immunoprofiling of Large-Scale Tuberculosis Dataset at Single Cell Resolution Reveals a CD81 γδ T Cell Population Associated with Latency.

Tuberculosis (TB) remains one of the leading causes of death among infectious diseases, with 10.6 million new cases and 1.3 million deaths reported in 2022, according to the most recent WHO report.

An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.

Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the gene of (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial as well as primary cells infected with virulent Mtb.

Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data Reveals Memory-like NK Cell Subset Associated with Latency.

Natural killer (NK) cells are innate-like lymphocytes that belong to the family of type-1 innate lymphoid cells and rapidly respond to virus-infected and tumor cells. In this study, we have combined scRNA-seq data and bulk RNA-seq data to define the phenotypic and molecular characteristics of peripheral blood NK cells. While the role of NK cells in immune surveillance against virus infections and tumors has been well established, their contribution to protective responses to other intracellular microorganisms, such as (Mtb), is still poorly understood.

Delivery of epitopes by adenylate cyclase toxoid expands HLA-E-restricted cytotoxic CD8 T cells.

Introduction: Tuberculosis (TB) remains the first cause of death from infection caused by a bacterial pathogen. Chemotherapy does not eradicate (Mtb) from human lungs, and the pathogen causes a latent tuberculosis infection that cannot be prevented by the currently available Bacille Calmette Guerin (BCG) vaccine, which is ineffective in the prevention of pulmonary TB in adults. HLA-E-restricted CD8+ T lymphocytes are essential players in protective immune responses against Mtb.

Correction: Shekarkar Azgomi et al. A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report. 2021, , 1576.

In the original publication, there was a mistake in Figure 1A, as published [...

Emerging Roles of Cells and Molecules of Innate Immunity in Alzheimer's Disease.

The inflammatory response that marks Alzheimer's disease (neuroinflammation) is considered a double-edged sword. Microglia have been shown to play a protective role at the beginning of the disease. Still, persistent harmful stimuli further activate microglia, inducing an exacerbating inflammatory process which impairs β-amyloid peptide clearance capability and leads to neurotoxicity and neurodegeneration.

B-Cell Receptor Signaling Is Thought to Be a Bridge between Primary Sjogren Syndrome and Diffuse Large B-Cell Lymphoma.

Primary Sjogren syndrome (pSS) is the second most common autoimmune disorder worldwide, which, in the worst scenario, progresses to Non-Hodgkin Lymphoma (NHL). Despite extensive studies, there is still a lack of knowledge about developing pSS for NHL. This study focused on cells' signaling in pSS progression to the NHL type of diffuse large B-cell lymphoma (DLBCL).

The Abundance of Tumor-Infiltrating CD8 Tissue Resident Memory T Lymphocytes Correlates with Patient Survival in Glioblastoma.

Glial tumors alone account for 40% of all CNS tumors and present a low survival rate. The tumor microenvironment is a critical regulator of tumor progression and therapeutic effectiveness in glioma. Growing evidence from numerous studies of human solid tumor-infiltrating CD8 T cells indicates that tissue-resident memory T cells (TRM) represent a substantial subpopulation of tumor-infiltrating lymphocytes (TILs).

Impact of Infection on Human B Cell Compartment and Antibody Responses.

Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of . Cellular immunity has a pivotal role against infection, but the role of humoral immunity is still controversial.

Interleukin-6 Is a Promising Marker of COVID-19 in Children: A Case Series of 2 Brothers with Severe COVID-19 Pneumonia.

BACKGROUND To date, Coronavirus disease 2019 (COVID-19) remains a global health concern, with fatalities mostly in older age groups with underlying medical conditions, while children are less likely to manifest severe symptoms. CASE REPORT We describe the clinical cases of 2 brothers admitted to our Children's Hospital for persistent fever and cough during the COVID-19 pandemic. Case 1.

Phenotypic and Immunometabolic Aspects on Stem Cell Memory and Resident Memory CD8 T Cells.

The immune system, smartly and surprisingly, saves the exposure of a particular pathogen in its memory and reacts to the pathogen very rapidly, preventing serious diseases. Immunologists have long been fascinated by understanding the ability to recall and respond faster and more vigorously to a pathogen, known as "memory". T-cell populations can be better described by using more sophisticated techniques to define phenotype, transcriptional and epigenetic signatures and metabolic pathways (single-cell resolution), which uncovered the heterogeneity of the memory T-compartment.

Metabolic Reprogramming of Innate Immune Cells as a Possible Source of New Therapeutic Approaches in Autoimmunity.

Immune cells undergo different metabolic pathways or immunometabolisms to interact with various antigens. Immunometabolism links immunological and metabolic processes and is critical for innate and adaptive immunity. Although metabolic reprogramming is necessary for cell differentiation and proliferation, it may mediate the imbalance of immune homeostasis, leading to the pathogenesis and development of some diseases, such as autoimmune diseases.

Interleukin 9 neutralisation reduces collagen-induced arthritis severity in mouse models.

Objectives: Interleukin 9 (IL-9) is a mediator of tissue damage in several inflammatory diseases. In this study we aimed to evaluate the effects of in vivo IL-9 neutralisation in mice developing collagen induced arthritis (CIA).

Methods: DBA/1 were immunised with collagen in Freund's complete adjuvant (CFA) to induce arthritis.

Platelets accumulate in lung lesions of tuberculosis patients and inhibit T-cell responses and Mycobacterium tuberculosis replication in macrophages.

Platelets regulate human inflammatory responses that lead to disease. However, the role of platelets in tuberculosis (TB) pathogenesis is still unclear. Here, we show that patients with active TB have a high number of platelets in peripheral blood and a low number of lymphocytes leading to a high platelets to lymphocytes ratio (PL ratio).

Immunity and Nutrition: The Right Balance in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an increasingly urgent medical problem that strongly impairs quality of life for patients. A global rise in incidence has been observed over the last few decades, with the highest incidence rates recorded in North America and Europe. Still, an increased incidence has been reported in the last ten years in newly industrialized countries in Asia, including China and India, both with more than one billion inhabitants.

Phosphatidylserine Liposomes Reduce Inflammatory Response, Mycobacterial Viability, and HIV Replication in Coinfected Human Macrophages.

Chronic immune activation is the key pathogenetic event of Mycobacterium tuberculosis-human immunodeficiency virus (HIV) coinfection. We assessed the therapeutic value of phosphatidylserine-liposome (PS-L) in an in vitro model of M. tuberculosis-HIV coinfection.

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways.

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions.

A Rapid and Simple Multiparameter Assay to Quantify Spike-Specific CD4 and CD8 T Cells after SARS-CoV-2 Vaccination: A Preliminary Report.

mRNA and Adenovirus vaccines for COVID-19 are used to induce humoral and cell-mediated immunity, with the aim to generate both SARS-CoV-2 B and T memory cells. In present study, we described a simple assay to detect and quantify Spike-specific CD4 and CD8 T cell responses induced by vaccination in healthy donors and in subjects with B cell compart impairment, in which antibody response is absent due to primary immunodeficiencies or CD20 depleting therapy. We detect and quantified memory T cell immune responses against SARS-CoV-2 evocated by vaccination in both groups, irrespective to the humoral response.

LIODetect®TB-ST: Evaluation of novel blood test for a rapid diagnosis of active pulmonary and extra-pulmonary tuberculosis in IGRA confirmed patients.

Because of the current limits of immunological tests in the diagnosis of tuberculosis there is a need to identify new and rapid tests that can be carried out on a large scale in endemic countries and useful in the identification of infected subjects, but also able to discriminate those with latent infection from subjects with active. We have taken into consideration and analysed the LIODetect®TB-ST Tuberculosis Rapid Test, a membrane test for the qualitative detection of specific IgG, IgA, and IgM antibodies against Mycobacterium tuberculosis, performed on serum, plasma, or whole blood.85 samples positive to QuantiFERON TB-GOLD PLUS test were processed using this test and the results obtained were concordant with clinical diagnosis.

Role of hematopoietic cells in Mycobacterium tuberculosis infection.

Tuberculosis remains one of the most significant causes of mortality worldwide and the current situation shows a re-emergence of TB due to the emergence of new antibiotic-resistant strains and the widespread of disease caused by immunodeficiencies. For these reasons, a big effort is made to improve the therapeutic strategies against Mycobacterium tuberculosis and to perform new therapeutic and diagnostic strategies. This review analyzes the various hematopoietic populations, their role and the different changes they undergo during Mycobacterium tuberculosis infection or disease.

Immune Response to Tick-Borne Hemoparasites: Host Adaptive Immune Response Mechanisms as Potential Targets for Therapies and Vaccines.

Tick-transmitted pathogens cause infectious diseases in both humans and animals. Different types of adaptive immune mechanisms could be induced in hosts by these microorganisms, triggered either directly by pathogen antigens or indirectly through soluble factors, such as cytokines and/or chemokines, secreted by host cells as response. Adaptive immunity effectors, such as antibody secretion and cytotoxic and/or T helper cell responses, are mainly involved in the late and long-lasting protective immune response.

Harnessing Unconventional T Cells for Immunotherapy of Tuberculosis.

Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. bacillus Calmette-Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection.