Induction of human regulatory innate lymphoid cells from group 2 innate lymphoid cells by retinoic acid.

Background: Group 2 innate lymphoid cells (ILC2s) play critical roles in induction and exacerbation of allergic airway inflammation. Thus clarification of the mechanisms that underlie regulation of ILC2 activation has received significant attention. Although innate lymphoid cells are divided into 3 major subsets that mirror helper effector T-cell subsets, counterpart subsets of regulatory T cells have not been well characterized.

Rationale for enteroviral vaccination and antiviral therapies in human type 1 diabetes.

In type 1 diabetes, pancreatic beta cells are destroyed by chronic autoimmune responses. The disease develops in genetically susceptible individuals, but a role for environmental factors has been postulated. Viral infections have long been considered as candidates for environmental triggers but, given the lack of evidence for an acute, widespread, cytopathic effect in the pancreas in type 1 diabetes or for a closely related temporal association of diabetes onset with such infections, a role for viruses in type 1 diabetes remains unproven.

Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus-associated syndromes.

Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%-40% for HPS. Puumala virus (PUUV) is the most common HFRS-causing hantavirus in Europe.

Taxonomy of the order Bunyavirales: second update 2018.

In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Daily Nutritional Supplementation with Vitamin D₃ and Phenylbutyrate to Treatment-Naïve HIV Patients Tested in a Randomized Placebo-Controlled Trial.

Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD₃) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD₃ (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, = 197) and per-protocol ( = 173) analyses.

Cytokine-induced endogenous production of prostaglandin D is essential for human group 2 innate lymphoid cell activation.

Background: Group 2 innate lymphoid cells (ILC2s) play a key role in the initiation and maintenance of type 2 immune responses. The prostaglandin (PG) D-chemoattractant receptor-homologous molecule expressed on T2 cells (CRTH2) receptor axis potently induces cytokine production and ILC2 migration.

Objective: We set out to examine PG production in human ILC2s and the implications of such endogenous production on ILC2 function.

Group A Streptococcal DNase Sda1 Impairs Plasmacytoid Dendritic Cells' Type 1 Interferon Response.

Group A Streptococcus causes severe invasive infections, including necrotizing fasciitis. The expression of an array of virulence factors targeting specific host immune functions impedes successful bacterial clearance. The virulence factor streptococcal DNase Sda1 was previously shown to interfere with the entrapment of bacteria through neutrophil extracellular traps and TLR9 signaling.

Everything in its right place: resident memory CD8+ T cell immunosurveillance of HIV infection.

Purpose Of Review: To introduce emerging concepts in tissue resident CD8 T cell immunosurveillance and their relevance to control HIV infection.

Recent Findings: It is well appreciated that HIV preferentially infects and persists in CD4 T cells located in gut and in lymphoid tissue, yet the majority of known immunological correlates of HIV control are derived from peripheral blood. Instead, tissue-based immunological surveillance likely dictates the course of infection.

Distinct Alterations in the Composition of Mucosal Innate Lymphoid Cells in Newly Diagnosed and Established Crohn's Disease and Ulcerative Colitis.

Background And Aims: Innate lymphoid cells [ILC] have been suggested to play a role in inflammatory bowel disease [IBD]. Here, we investigated the ILC compartment in intestinal biopsies and blood from distinct patient groups with Crohn's disease [CD] and ulcerative colitis [UC], either newly diagnosed or with disease established for at least 1 year. This approach allowed us to simultaneously investigate temporal, disease-specific, and tissue-specific changes in ILC composition in IBD.

Oxysterols in intestinal immunity and inflammation.

Cholesterol is an essential molecule for life. It is a component of the cell membrane, and it is a precursor molecule for bile acids, vitamin D and steroid hormones. Cholesterol is actively metabolized, but the impact of endogenous cholesterol metabolites on immune function, especially in the intestine, is poorly understood.

The CD4CD8 MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8 MAIT cell pool.

Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the MHC class I-like protein MR1. Human MAIT cells predominantly express the CD8α coreceptor (CD8), with a smaller subset lacking both CD4 and CD8 (double-negative, DN). However, it is unclear if these two MAIT cell subpopulations distinguished by CD8α represent functionally distinct subsets.

Innovative therapy, monoclonal antibodies, and beyond: Highlights from the eighth annual meeting.

The eighth annual conference of "Innovative therapy, monoclonal antibodies, and beyond" was held in Milan on Jan. 26, 2018, and hosted by Fondazione IRCCS-Istituto Nazionale dei Tumori (Fondazione IRCCS INT). The conference was divided into two main scientific sessions, of i) pre-clinical assays and novel biotargets, and ii) clinical translation, as well as a third session of presentations from young investigators, which focused on recent achievements within Fondazione IRCCS INT on immunotherapy and targeted therapies.

An Optimized Protocol for the Isolation and Functional Analysis of Human Lung Mast Cells.

Mast cells are tissue-resident inflammatory cells defined by their high granularity and surface expression of the high-affinity IgE receptor, FcεRI, and CD117/KIT, the receptor for stem cell factor (SCF). There is a considerable heterogeneity among mast cells, both phenotypically and functionally. Human mast cells are generally divided into two main subtypes based on their protease content; the mucosa-associated MC (tryptase positive and chymase negative mast cell) and the connective tissue associated-residing MC (tryptase and chymase positive mast cell).

Cell-Mediated Immune Responses and Immunopathogenesis of Human Tick-Borne Encephalitis Virus-Infection.

Tick-borne encephalitis virus (TBEV) is a flavivirus that belongs to the family. TBEV is transmitted to humans primarily from infected ticks. The virus causes tick-borne encephalitis (TBE), an acute viral disease that affects the central nervous system (CNS).

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells.

Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts.

High-Resolution Genetic and Phenotypic Analysis of KIR2DL1 Alleles and Their Association with Pre-Eclampsia.

Killer-cell Ig-like receptor (KIR) genes are inherited as haplotypes. They are expressed by NK cells and linked to outcomes of infectious diseases and pregnancy in humans. Understanding how genotype relates to phenotype is difficult because of the extensive diversity of the KIR family.

High HMGB1 levels in sputum are related to pneumococcal bacteraemia but not to disease severity in community-acquired pneumonia.

During bacterial infections, damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) activate immune cells. Here, we investigated whether plasma and sputum levels of High Mobility Group Box 1 (HMGB1), a prototypic DAMP, are associated with disease severity and aetiology in community-acquired pneumonia (CAP). In addition, in patients with pneumococcal CAP, the impact of the level of sputum lytA DNA load, a PAMP, was investigated.

Novel Models to Study Stromal Cell-Leukocyte Interactions in Health and Disease.

To study human immunology in general and stromal immunology in particular, it is highly motivated to move from monolayers to 3D cultures, such as organotypic models, that better mimic the function of living tissue. These models can potentially contain most if not all cell types present in tissues, in combination with different extracellular matrix components that can critically affect cell phenotype. Besides their well-established use in studies of tissue-specific cells, such as epithelial cells, endothelial cells and stromal fibroblasts in combination with extracellular components, these models have also been shown to be valuable to study how tissue participates in the regulation of leukocyte differentiation and function.

Cripto-1 Plasmid DNA Vaccination Targets Metastasis and Cancer Stem Cells in Murine Mammary Carcinoma.

Metastatic breast cancer is a fatal disease that responds poorly to treatment. Cancer vaccines targeting antigens expressed by metastatic breast cancer cells and cancer stem cells could function as anticancer therapies. Cripto-1 is an oncofetal protein overexpressed in invasive breast cancer and cancer-initiating cells.

Factors Influencing Functional Heterogeneity in Human Mucosa-Associated Invariant T Cells.

Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the monomorphic MHC class I-related (MR1) molecule. Despite the high level of evolutionary conservation of MR1 and the limited diversity of known antigens, human MAIT cells and their responses may not be as homogeneous as previously thought. Here, we review recent findings indicating that MAIT cells display microbe-specific response patterns with multiple layers of heterogeneity.

Natural killer cell specificity for viral infections.

Natural killer (NK) cells are lymphocytes that contribute to the early immune responses to viruses. NK cells are innate immune cells that do not express rearranged antigen receptors but sense their environment via receptors for pro-inflammatory cytokines, as well as via germline-encoded activating receptors specific for danger or pathogen signals. A group of such activating receptors is stochastically expressed by certain subsets within the NK cell compartment.

Human polyspecific immunoglobulin attenuates group A streptococcal virulence factor activity and reduces disease severity in a murine necrotizing fasciitis model.

Objectives: Streptococcus pyogenes causes life-threatening invasive infections including necrotizing fasciitis (NF). Current treatment guidelines recommend the use of a cell-wall-active antibiotic combined with a protein synthesis inhibitor and surgical debridement in NF patients. Adjunctive therapy with intravenous immunoglobulin (IVIG) has been proposed for superantigen-associated streptococcal toxic shock syndrome.

Proteome analysis of human CD56 NK cells reveals a homogeneous phenotype surprisingly similar to CD56 NK cells.

NK cells lacking CD56 (CD56 ) were first identified in chronic HIV-1 infection. However, CD56 NK cells also exist in healthy individuals, albeit in significantly lower numbers. Here, we provide an extensive proteomic characterisation of human CD56 peripheral blood NK cells of healthy donors and compare them to their CD56 and CD56 counterparts.

MMP-12 and S100s in saliva reflect different aspects of periodontal inflammation.

Matrix metalloproteinase (MMP)-12, S100A8/A9, and S100A12 are involved in innate immune responses. We addressed whether different aspects of oral health and non-disease-related covariates influence their levels in saliva. 436 participants were clinically examined, completed a health questionnaire, and provided stimulated saliva.