The roles for innate lymphoid cells in the human immune system.

From constituting a novel and obscure cell population, innate lymphoid cells (ILCs) are now accepted as a self-evident part of the immune system, contributing with unique and complementary functions to immunity by production of effector cytokines and interaction with other cell types. In this review, we discuss the redundant and complementary roles of the highly plastic human ILCs and their interaction with other immune cells with the ultimate aim of placing ILCs in a wider context within the human immune system.

Chronic hepatitis C virus infection irreversibly impacts human natural killer cell repertoire diversity.

Diversity is a central requirement for the immune system's capacity to adequately clear a variety of different infections. As such, natural killer (NK) cells represent a highly diverse population of innate lymphocytes important in the early response against viruses. Yet, the extent to which a chronic pathogen affects NK cell diversity is largely unknown.

Vitamin D₃ Status and the Association with Human Cathelicidin Expression in Patients with Different Clinical Forms of Active Tuberculosis.

Low vitamin D (vitD₃) is one of the most common nutritional deficiencies in the world known to be associated with numerous medical conditions including infections such as tuberculosis (TB). In this study, vitD₃ status and its association with the antimicrobial peptide, human cathelicidin (LL-37), was investigated in Ethiopian patients with different clinical forms of TB. Patients with active TB ( = 77) and non-TB controls ( = 78) were enrolled in Ethiopia, while another group of non-TB controls ( = 62) was from Sweden.

Human Organotypic Respiratory Models.

Biomedical research aiming to understand the molecular basis of human lung tissue development, homeostasis and disease, or to develop new therapies for human respiratory diseases, requires models that faithfully recapitulate the human condition. This has stimulated biologists and engineers to develop in vitro organotypic models mimicking human respiratory tissues. In this chapter, we provide examples of different types of model systems ranging from simple unicellular cultures to more complex multicellular systems.

Perspectives for personalized therapy for patients with multidrug-resistant tuberculosis.

According to the World Health Organization (WHO), tuberculosis is the leading cause of death attributed to a single microbial pathogen worldwide. In addition to the large number of patients affected by tuberculosis, the emergence of Mycobacterium tuberculosis drug-resistance is complicating tuberculosis control in many high-burden countries. During the past 5 years, the global number of patients identified with multidrug-resistant tuberculosis (MDR-TB), defined as bacillary resistance at least against rifampicin and isoniazid, the two most active drugs in a treatment regimen, has increased by more than 20% annually.

Vitamin D and tuberculosis: where next?

Tuberculosis (TB) has troubled mankind for millennia, but current treatment strategies are long and complicated and the disease remains a major global health problem. The risk of Mycobacterium tuberculosis (Mtb) infection or progression of active TB disease is elevated in individuals with vitamin D deficiency. High-dose vitamin D was used to treat TB in the preantibiotic era, and in vitro experimental data show that vitamin D supports innate immune responses that restrict growth of Mtb.

Friends and foes of tuberculosis: modulation of protective immunity.

Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN-γ producing CD4 T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T-cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity.

Spatial distribution and function of T follicular regulatory cells in human lymph nodes.

T follicular regulatory (Tfr) cells are a population of CD4 T cells that express regulatory T cell markers and have been shown to suppress humoral immunity. However, the precise mechanisms and location of Tfr-mediated suppression in the lymph node (LN) microenvironment are unknown. Using highly multiplexed quantitative imaging and functional assays, we examined the spatial distribution, suppressive function, and preferred interacting partners of Tfr cells in human mesenteric LNs.

Medical phycology 2017.

In 2014, ISHAM formed a new working group: "Medical Phycology: Protothecosis and Chlorellosis." The purpose of this working group is to help facilitate collaboration and communication among people interested in the pathogenic algae, to share ideas and work together. Here we present reports on recent work we have done in five areas.

Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B.

Background & Aims: Treatment with nucleos(t)ide analogues (NA) leads to hepatitis B virus (HBV) DNA suppression in most patients with chronic hepatitis B (CHB), but HBV surface antigen (HBsAg) loss rates are low. Upon NA discontinuation, HBV DNA can return rapidly with ensuing alanine aminotransferase flares and induction of cytokines. Several studies reported higher HBsAg loss rates after stopping therapy, but at present it is unclear if cell-mediated immune responses are altered after treatment discontinuation.

Severely Impaired Control of Bacterial Infections in a Patient With Cystic Fibrosis Defective in Mucosal-Associated Invariant T Cells.

Here we report a unique case of a patient with cystic fibrosis characterized by severely impaired control of bacterial respiratory infections. This patient's susceptibility to such infections was much worse than expected from a cystic fibrosis clinical perspective, and he died at age 22 years despite extensive efforts and massive use of antibiotics. We found that this severe condition was associated with a near-complete deficiency in circulating mucosal-associated invariant T (MAIT) cells as measured at several time points.

Daily adjunctive therapy with vitamin D and phenylbutyrate supports clinical recovery from pulmonary tuberculosis: a randomized controlled trial in Ethiopia.

Objective: Immunotherapy using vitamin D (vitD ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD + PBA enhanced clinical recovery from pulmonary tuberculosis (TB).

Methods: A randomized controlled trial was conducted in Addis Ababa, Ethiopia.

IL13Rα2 expression identifies tissue-resident IL-22-producing PLZF innate T cells in the human liver.

Innate lymphocytes are selectively enriched in the liver where they have important roles in liver immunology. Murine studies have shown that type I NKT cells can promote liver inflammation, whereas type II NKT cells have an anti-inflammatory role. In humans, type II NKT cells were found to accumulate in the gut during inflammation and IL13Rα2 was proposed as a marker for these cells.

Influenza-Activated ILC1s Contribute to Antiviral Immunity Partially Influenced by Differential GITR Expression.

Innate lymphoid cells (ILCs) represent diversified subsets of effector cells as well as immune regulators of mucosal immunity and are classified into group 1 ILCs, group 2 ILCs, and group 3 ILCs. Group 1 ILCs encompass natural killer (NK) cells and non-NK ILCs (ILC1s) and mediate their functionality the rapid production of IFN-γ and TNF-α. The current knowledge of ILC1s mainly associates them to inflammatory processes.

IL-7 treatment supports CD8+ mucosa-associated invariant T-cell restoration in HIV-1-infected patients on antiretroviral therapy.

: Chronic HIV-1 infection is associated with lower frequencies and functional impairment of mucosa-associated invariant T (MAIT) cells. We evaluated IL-7 treatment to restore MAIT cells in peripheral blood of chronically HIV-1-infected individuals on antiretroviral therapy. IL-7 led to increased relative and absolute levels of MAIT cells, and this expansion occurred primarily in the CD8 subset.

Protein SIC Secreted from Forms Complexes with Extracellular Histones That Boost Cytokine Production.

Innate immunity relies on an effective recognition of the pathogenic microorganism as well as on endogenous danger signals. While bacteria in concert with their secreted virulence factors can cause a number of inflammatory reactions, danger signals released at the site of infection may in addition determine the amplitude of such responses and influence the outcome of the disease. Here, we report that protein SIC, Streptococcal Inhibitor of Complement, an abundant secreted protein from , binds to extracellular histones, a group of danger signals released during necrotizing tissue damage.

Increased NK Cell Function After Cessation of Long-Term Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Is Associated With Liver Damage and HBsAg Loss.

Background: Treatment with nucleos(t)ide analogues (NA) suppresses hepatitis B virus (HBV) DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, some hepatitis B e antigen (HBeAg)-negative CHB patients experience hepatitis B s antigen (HBsAg) loss. Cellular immune responses, including natural killer (NK) cell responses, explaining virological events following NA treatment cessation remain elusive.

Complete Remission with Reduction of High-Risk Clones following Haploidentical NK-Cell Therapy against MDS and AML.

To evaluate the safety, efficacy, and immunobiological correlates of allogeneic NK-cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and AML patients. Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL2-activated haploidentical NK cells. NK-cell infusions were well-tolerated, with only transient adverse events observed in the 16 patients.

New Coxsackievirus 2A and 3C protease antibodies for virus detection and discovery of pathogenic mechanisms.

Enteroviruses (EVs), such as the Coxsackie B-viruses (CVBs), are common human pathogens, which can cause severe diseases including meningitis, myocarditis and neonatal sepsis. EVs encode two proteases (2A and 3C), which perform the proteolytic cleavage of the CVB polyprotein and also cleave host cell proteins to facilitate viral replication. The 2A cause direct damage to the infected heart and tools to investigate 2A and 3C expression may contribute new knowledge on virus-induced pathologies.

Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.

Human immunodeficiency virus type-1 (HIV-1) elite controllers (ELCs) represent a unique population that control viral replication in the absence of antiretroviral therapy (cART). It is well established that expression of multiple inhibitory receptors on CD8+ T cells is associated with HIV-1 disease progression. However, whether reduced co-expression of inhibitory receptors on CD4+ T cells is linked to natural viral control and slow HIV-1 disease progression remains undefined.

Prostaglandin E suppresses hCAP18/LL-37 expression in human macrophages via EP2/EP4: implications for treatment of Mycobacterium tuberculosis infection.

Prostaglandin (PG)E is an arachidonic acid-derived lipid mediator that plays an important role in inflammation and immunity. In this study, we demonstrate that PGE suppresses basal and 1,25-dihydroxy vitamin D (VD)-induced expression of hCAP18/LL-37 via E prostanoid (EP)2 and EP4 receptors. In humans, VD up-regulates vitamin D receptor (VDR) expression and promotes transcription of the cathelicidin hCAP18/LL-37 gene, whereas PGE counteracts this effect.

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC).