Annalisa Barera

Selective Depression of Interferon-γ and Granulysin Production with Increase of Proliferative Response by Vγ9/Vδ2 T Cells in Children with Tuberculosis

Vgamma9/Vdelta2 T cells can contribute to protective immune response against Mycobacterium tuberculosis, although the extent to which and mechanisms by which they could actually protect against human tuberculosis remain unclear. We have previously reported that Vgamma9/Vdelta2 T cells from tuberculin purified protein derivative (PPD)-positive children, either healthy or affected by different clinical forms of tuberculosis, strongly proliferate to different phosphoantigens in vitro, whereas Vgamma9/Vdelta2 T cells from PPD-negative healthy subjects proliferate very poorly. We report here that Vgamma9/Vdelta2 T cells from tuberculous children have an increased proliferative activity, but decreased interferon (IFN)-gamma production and granulysin expression. After successful chemotherapy, the Vgamma9/Vdelta2 T cell proliferative response strongly decreased, whereas IFN-gamma and granulysin production consistently increased. Disease-associated changes in Vgamma9/Vdelta2 T cell effector functions in patients with tuberculosis are consistent with the possibility that these T cells may play a protective role in immune response against M. tuberculosis infection.

Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: Use of insulin to attenuate metformin's effect.

Clinical and experimental biomedical studies have shown Type 2 diabetes mellitus (T2DM) to be a risk factor for the development of Alzheimers disease (AD). This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on β-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models. Furthermore, the protective role of insulin against metformin is also demonstrated. In LAN5 neuroblastoma cells, metformin increases APP and presenilin levels, proteins involved in AD. Overexpression of APP and presenilin 1 (Pres 1) increases APP cleavage and intracellular accumulation of β-amyloid peptide (Aβ), which, in turn, promotes aggregation of Aβ. In the experimental conditions utilized the drug causes oxidative stress, mitochondrial damage, decrease of Hexokinase-II levels and cytochrome C release, all of which lead to cell death. Several changes in oxidative stress-related genes following metformin treatment were detected by PCR arrays specific for the oxidative stress pathway. These effects of metformin were found to be antagonized by the addition of insulin, which reduced Aβ levels, oxidative stress, mitochondrial dysfunction and cell death. Similarly, antioxidant molecules, such as ferulic acid and curcumin, are able to revert metformins effect. Comparable results were obtained using peripheral blood mononuclear cells. Finally, the involvement of NF-κB transcription factor in regulating APP and Pres 1 expression was investigated. Upon metformin treatment, NF-κB is activated and translocates from the cytoplasm to the nucleus, where it induces increased APP and Pres 1 transcription. The use of Bay11-7085 inhibitor suppressed the effect of metformin on APP and Pres 1 expression.

Cytokine profile, HLA restriction and TCR sequence analysis of human CD4+ T clones specific for an immunodominant epitope of Mycobacterium tuberculosis 16-kDa protein

The identification of immunodominant and universal mycobacterial peptides could be applied to vaccine design and have an employment as diagnostic reagents. In this paper we have investigated the fine specificity, clonal composition and HLA class II restriction of CD4+ T cell clones specific for an immunodominant epitope spanning amino acids 91–110 of the 16‐kDa protein of Mycobacterium tuberculosis. Twenty‐one of the tested 28 clones had a Th1 profile, while seven clones had a Th0 profile. None of the clones had a Th2 profile. While the TCR AV gene usage of the clones was heterogeneous, a dominant TCR BV2 gene family was used by 18 of the 28 clones. The CDR3 regions of BV2+ T cell clones showed variation in lengths, but a putative common motif R‐L/V‐G/S‐Y/W‐E/D was detected in 13 of the 18 clones. Moreover, the last two to three residues of the putative CDR3 loops, encoded by conserved BJ sequences, could also play a role in peptide recognition. Antibody blockade and fine restriction analysis using HLA‐DR homozygous antigen‐presenting cells established that 16 of 18 BV2+ peptide‐specific clones were DR restricted and two clones were DR‐DQ and DR‐DP restricted. Additionally, five of the 18 TCRBV2+ clones recognized peptide 91–110 in association with both parental and diverse HLA‐DR molecules, indicating their promiscuous recognition pattern. The ability of peptide 91–110 to bind a wide range of HLA‐DR molecules, and to stimulate a Th1‐type interferon (IFN)‐γ response more readily, encourage the use of this peptide as a subunit vaccine component.

Mediterranean Diet and Healthy Ageing: A Sicilian Perspective

Traditional Mediterranean diet (MedDiet) is a common dietary pattern characterizing a lifestyle and culture proven to contribute to better health and quality of life in Mediterranean countries. By analyzing the diet of centenarians from the Sicani Mountains and eating habits of inhabitants of Palermo, it is reported that a close adherence to MedDiet is observed in the countryside, whereas in big towns this adherence is not so close. This has an effect on the rates of mortality at old age (and reciprocally longevity) that are lower in the countryside than in big towns. Concerning the health effects of the diet, the low content of animal protein and the low glycaemic index of the Sicilian MedDiet might directly modulate the insulin/IGF-1 and the mTOR pathways, known to be involved in ageing and longevity. In particular, the reduction of animal protein intake may significantly reduce serum IGF-1 concentrations and inhibit mTOR activity with a down-regulation of the signal that leads to the activation of FOXO3A and, consequently, to the transcription of homeostatic genes that favour longevity. The down-regulation of both IGF-1 and mTORC1 also induces an anti-inflammatory effect. In addition to the effects on sensing pathways, many single components of MedDiet are known to have positive effects on health, reducing inflammation, optimizing cholesterol and other important risk factors of age-related diseases. However, a key role is played by polyphenols represented in high amount in the Sicilian MedDiet (in particular in extra virgin olive oil) that can work as hormetins that provide an environmental chemical signature regulating stress resistance pathways such as nuclear factor erythroid 2-related factor 2.

Inflammatory Mediators as Biomarkers in Brain Disorders

Neurodegenerative diseases such as Alzheimer, Parkinson, amyotrophic lateral sclerosis, and Huntington are incurable and debilitating conditions that result in progressive death of the neurons. The definite diagnosis of a neurodegenerative disorder is disadvantaged by the difficulty in obtaining biopsies and thereby to validate the clinical diagnosis with pathological results. Biomarkers are valuable indicators for detecting different phases of a disease such as prevention, early onset, treatment, progression, and monitoring the effect of pharmacological responses to a therapeutic intervention. Inflammation occurs in neurodegenerative diseases, and identification and validation of molecules involved in this process could be a strategy for finding new biomarkers. The ideal inflammatory biomarker needs to be easily measurable, must be reproducible, not subject to wide variation in the population, and unaffected by external factors. Our review summarizes the most important inflammation biomarkers currently available, whose specificity could be utilized for identifying and monitoring distinctive phases of different neurodegenerative diseases.

Mediterranean diet and longevity: an example of nutraceuticals?

The Mediterranean diet (Mediet) is an eating pattern characterizing a lifestyle and culture that has been reported to contribute to better health and quality of life. The Mediet reflects food patterns typical of Mediterranean regions, where olive oil plays an essential role in the food pyramid. Olive oil is located in the middle and it is considered the principal source of dietary fat because of its high nutritional quality (particularly extra virgin olive oil). Several studies have shown the effect of the Mediet on healthy status by lowering the rates of coronary heart disease, certain cancers, and some other age-related chronic diseases. Although the scientific literature regarding diet and life span is complex and with different opinions, there are studies that demonstrate the beneficial effects of the Mediet on longevity. Therefore, the Mediet may be considered as including several nutraceuticals that favourably influence health. In the present review we discuss two Mediterranean populations from the island of Ikaria (Greece) and the Sicani Mounts (Sicily, Italy) whose longevity is attributed to a close adherence to the Mediet.

β-glucans: ex vivo inflammatory and oxidative stress results after pasta intake

BackgroundIt is well known that Mediterranean Diet can positively influence the health of each individual, in particular it is know that fibers have an important role. However, in Mediterranean cities most people do not have a close adherence to Mediterranean diet. Thus, in our study, we considered fibers like β-glucans that have been added to pasta with a percentage of 6 %. Our study aimed to evaluate the capacity of β-glucans intake on oxidative stress and inflammation in a cohort of middle aged slightly overweight subjects.MethodsWe used a longitudinal study design. The study lasted 30 days during which time, each participant acted with no food restriction. Participants underwent morning fasting blood venous sample for blood chemistry and other biological parameters at the beginning of the study and after 30 days of pasta supplemented with 6 % of β-glucan intake 4 times a week. We performed anthropometric, biochemical, oxidative stress and cytokine analysis at the beginning and the end of study.ResultsAfter the 30 days of pasta intake we obtained a significant decrease of LDL-cholesterol, IL-6 and AGEs levels.ConclusionThe results confirmed a capacity of β-glucans intake to lower oxidative stress. Additional longitudinal observation on community-based cohorts are needed to confirm these data and investigate the biological mechanisms through which effects are induced, and to fully explore the therapeutic potential of β-glucans.

A Human Leucocyte Antigen‐DR1 Transgene Confers Susceptibility to Experimental Allergic Encephalomyelitis Elicited by an Epitope of Myelin Basic Protein

Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA‐restricted presentation of T‐cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA‐DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13–33, 87–106 and 139–154 bound by HLA‐DR1. We report here that HLA‐DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13–33 epitope induced a strong T helper 1 (Th1) response accompanied by high T‐cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139–154) or no disease (87–106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.

ESAT-6 Peptide Recognition by Bovine CD8 Lymphocytes of Naturally Infected Cows in Herds from Southern Italy

ABSTRACT The aim of this study was to define epitopes of Mycobacterium bovis from ESAT-6 (early secretory antigen of 6 kDa) recognized by CD8+ T lymphocytes from cows naturally infected with Mycobacterium bovis. We found that bovine CD8+ T cells recognized 10 out of 11 ESAT-6 peptides tested.

Contents Vol. 60, 2014

Clinical Section D. Aarsland, Stockholm J. Attems, Newcastle upon Tyne M. Burtscher, Innsbruck G. Del Giudice, Siena V.C. Emery, Guildford J.D. Erusalimsky, Cardiff L. Fontana, St. Louis, Mo. J.J. Goronzy, Stanford, Calif. U. Granacher, Potsdam S. Gravenstein, Cleveland, Ohio F. Kronenberg, Innsbruck T.F. Lue, San Francisco, Calif. A.B. Maier, Amsterdam J. Olshansky, Chicago, Ill. T.M. Stulnig, Vienna J. Tao, Guangzhou D.C. Willcox, Ginowan D. Ziegler, Düsseldorf Behavioural Science Section K.J. Anstey, Acton, A.C.T. L. Clare, Bangor X.-Q. Dong, Chicago, Ill. J.D. Henry, St. Lucia, Qld. T. Hess, Raleigh, N.C. S.M. Hofer, Victoria, B.C. C.A. Hoppmann, Vancouver, B.C. D.C. Park, Dallas, Tex. R. Schwendimann, Basel B.J. Small, Tampa, Fla.