Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions.

Macrophages fight infection and ensure tissue repair, often operating at nutrient-poor wound sites. We investigated the ability of human macrophages to metabolize glycogen. We observed that the cytokines GM-CSF and M-CSF plus IL-4 induced glycogenesis and the accumulation of glycogen by monocyte-derived macrophages.

Functional insights into human macrophage response against Scedosporium apiospermum and Scedosporium dehoogii.

Fungal infections caused by Scedosporium species are rising among immunocompromised and immunocompetent patients. Within the immunocompetent group, patients with cystic fibrosis (pwCF) are at high risk of developing a chronic airway colonization by these molds. While S.

IL-26 inhibits hepatitis C virus replication in hepatocytes.

Background & Aims: Interleukin-26 (IL-26) is a proinflammatory cytokine that has properties atypical for a cytokine, such as direct antibacterial activity and DNA-binding capacity. We previously observed an accumulation of IL-26 in fibrotic and inflammatory lesions in the livers of patients with chronic HCV infection and showed that infiltrating CD3 lymphocytes were the principal source of IL-26. Surprisingly, IL-26 was also detected in the cytoplasm of hepatocytes from HCV-infected patients, even though these cells do not produce IL-26, even when infected with HCV.

Acetoacetate protects macrophages from lactic acidosis-induced mitochondrial dysfunction by metabolic reprograming.

Lactic acidosis, the extracellular accumulation of lactate and protons, is a consequence of increased glycolysis triggered by insufficient oxygen supply to tissues. Macrophages are able to differentiate from monocytes under such acidotic conditions, and remain active in order to resolve the underlying injury. Here we show that, in lactic acidosis, human monocytes differentiating into macrophages are characterized by depolarized mitochondria, transient reduction of mitochondrial mass due to mitophagy, and a significant decrease in nutrient absorption.

Carrot Genotypes Contrasted by Root Color and Grown under Different Conditions Displayed Differential Pharmacological Profiles in Vascular and Metabolic Cells.

Carrots' genotype and growing conditions influence their potential properties to fight against cardiovascular and metabolic diseases. The present study evaluated the influence of carrot genotypes contrasted by root color (Bolero, Presto, Karotan, Deep Purple, Kintoki and Blanche des Vosges) growing under standard, water-restricted, biotic stress ( inoculation), and combined stress conditions (water restriction and inoculation). The effect of carrots' polyphenol and carotenoid content was assessed on endothelial and smooth muscle cells, hepatocytes, adipocytes and macrophages functions (oxidative stress, apoptosis, proliferation, lipid accumulation and inflammation).

Lactic Acidosis Together with GM-CSF and M-CSF Induces Human Macrophages toward an Inflammatory Protumor Phenotype.

In established tumors, tumor-associated macrophages (TAM) orchestrate nonresolving cancer-related inflammation and produce mediators favoring tumor growth, metastasis, and angiogenesis. However, the factors conferring inflammatory and protumor properties on human macrophages remain largely unknown. Most solid tumors have high lactate content.

Screening of ordinary commercial varieties of apple fruits under different storage conditions for their potential vascular and metabolic protective properties.

Epidemiological studies reported that apple consumption is associated with a decrease of cardiovascular and metabolic dysfunction, probably due to the polyphenols and fibers present in this fruit. The storage conditions and genetic origin of apples have been reported to influence their content and, as a consequence, their pharmacological properties. The present study evaluated the influence of varieties and storage conditions of traditional and highly appreciated apples including Gala, Golden Delicious, Granny Smith and Pink Lady varieties after harvest and storage under classic cold conditions, under a controlled atmosphere, or under extreme ultra-low oxygen conditions.

IL-26 Confers Proinflammatory Properties to Extracellular DNA.

In physiological conditions, self-DNA released by dying cells is not detected by intracellular DNA sensors. In chronic inflammatory disorders, unabated inflammation has been associated with a break in innate immune tolerance to self-DNA. However, extracellular DNA has to complex with DNA-binding molecules to gain access to intracellular DNA sensors.

Detection of Anti-Pentraxin-3 Autoantibodies in ANCA-Associated Vasculitis.

Objectives: Pentraxin 3 (PTX3), in common with myeloperoxidase and proteinase 3, is stored in human neutrophil granules and is expressed on apoptotic neutrophil surface. We therefore investigated the presence of anti-PTX3 autoantibodies (aAbs) in the sera of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients.

Methods: Presence of anti-PTX3 autoantibodies was analysed by a specific enzyme-linked immunosorbent assay in sera from 150 patients with microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), and in sera of 227 healthy subjects (HS), 40 systemic sclerosis (SSc) patients, and 25 giant cell arteritis patients (GCA).

Modulation of Cytokine Secretion Allows CD4 T Cells Secreting IL-10 and IL-17 to Simultaneously Participate in Maintaining Tolerance and Immunity.

CD4 T cells secreting IL-10 or IL-17 are frequent at mucosal sites, where their equilibrium is important for simultaneously maintaining tolerance and immunity to the resident microbiota. The mode of action of these cells, however, is as yet incompletely understood. In this study, we have combined ex vivo analysis of CD4 T cells producing IL-10 or/and IL-17 with assessment of clonal populations isolated ex vivo using a cytokine catch assay.

Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos+, but not natural Helios+, FOXP3+ Treg cells.

IL4I1 encodes an L-phenylalanine oxidase that inhibits T-cell proliferation. It has been recently reported that IL4I1 is expressed in TH17 cells as part of a mechanism that limits their pathogenicity. We have previously identified a population of human FOXP3(+) Treg cells that secrete IL-17 ex vivo; here, we addressed the expression of IL4I1 in that Treg-cell population.

CD4+ T effectors specific for the tumor antigen NY-ESO-1 are highly enriched at ovarian cancer sites and coexist with, but are distinct from, tumor-associated Treg.

Whereas tumor infiltration by T effectors is generally associated with a more favorable prognosis, the accumulation of CD4(+) regulatory T cells (Treg) within tumors is instead often associated with poor disease outcome. Because approaches to improve antitumor immunity aim, on one hand, at expanding tumor antigen-specific T cells and, on the other, at eliminating or inactivating Treg, an outstanding question is whether, and to what extent, tumor antigen-specific CD4(+) T effectors present at tumor sites overlap with tumor-associated Treg. Here, we used MHC class II/peptide tetramers incorporating an immunodominant peptide from the human tumor-specific antigen NY-ESO-1 to assess antigen-specific CD4(+) T cells among conventional CD4(+) T effectors and Treg at sites of ovarian cancer.

Expression of MAGE-A3/6 in primary breast cancer is associated with hormone receptor negative status, high histologic grade, and poor survival.

The cancer testis antigen (CTA), melanoma-associated antigen A3/6 (MAGE-A3/6), is expressed in human cancers of different histologic types, to variable extents, and is an important target for immunotherapy. In this study, to address the potential of MAGE-A3/6 as an immunotherapeutic target in breast cancer (BC), we assessed MAGE-A3/6 expression by PCR in a cohort of 362 primary BC tumors and analyzed the correlation between MAGE-A3/6 expression, tumors hormone receptor (HR) status, and other clinicopathologic features. We found expression of MAGE-A3/6 in 10% of primary BC tumors.

Human memory Helios- FOXP3+ regulatory T cells (Tregs) encompass induced Tregs that express Aiolos and respond to IL-1β by downregulating their suppressor functions.

FOXP3(+) regulatory T cells (Tregs) are critical regulators of self-tolerance and immune homeostasis. In mice and humans, two subsets of FOXP3(+) Tregs have been defined based on their differential expression of Helios, a transcription factor of the Ikaros family. Whereas the origin, specificity, and differential function of the two subsets are as yet a source of controversy, their characterization thus far has been limited by the absence of surface markers to distinguish them.

CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity.

Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape. One critical mechanism involves the accumulation of FOXP3(+) T regulatory cells (Treg), a class of suppressive T cells that prevent excessive tissue destruction caused by unchecked immune responses. Recent studies have revealed that FOXP3(+) Treg include distinct subsets specifically controlling over the corresponding effector subset.

Human T(H)17 immune cells specific for the tumor antigen MAGE-A3 convert to IFN-γ-secreting cells as they differentiate into effector T cells in vivo.

The role of T(H)17 cells in cancer is being investigated, but the existence of tumor antigen-specific T(H)17 cells has yet to be ascertained. Here, we report the first description of a spontaneous T(H)17 (IL-17(+)) response to the important tumor antigen MAGE-A3, which occurred concurrently with a T(H)1 (IFN-γ(+)) response in a lung cancer patient. MAGE-A3-specific interleukin (IL)-17(+) T cells were mainly CCR7(+) central memory T cells, whereas IFN-γ(+) cells were enriched for CCR7(-) effector memory T cells.

Antibody responses to NY-ESO-1 in primary breast cancer identify a subtype target for immunotherapy.

The highly immunogenic human tumor antigen NY-ESO-1 (ESO) is a target of choice for anti-cancer immune therapy. In this study, we assessed spontaneous antibody (Ab) responses to ESO in a large cohort of patients with primary breast cancer (BC) and addressed the correlation between the presence of anti-ESO Ab, the expression of ESO in the tumors and their characteristics. We found detectable Ab responses to ESO in 1% of the patients.

Assessment of vaccine-induced CD4 T cell responses to the 119-143 immunodominant region of the tumor-specific antigen NY-ESO-1 using DRB1*0101 tetramers.

Purpose: NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO(119-143) region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO(119-143) tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1).

Monitoring of NY-ESO-1 specific CD4+ T cells using molecularly defined MHC class II/His-tag-peptide tetramers.

MHC-peptide tetramers have become essential tools for T-cell analysis, but few MHC class II tetramers incorporating peptides from human tumor and self-antigens have been developed. Among limiting factors are the high polymorphism of class II molecules and the low binding capacity of the peptides. Here, we report the generation of molecularly defined tetramers using His-tagged peptides and isolation of folded MHC/peptide monomers by affinity purification.