Infection des cellules dendritiques périphériques du sang par le virus de l'hépatite C

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Artificial Immune Tissue using Self-Organizing Networks

As introduced by Bentley et al. (2005), artificial immune systems (AIS) are lacking tissue, which is present in one form or another in all living multi-cellular organisms. Some have argued that this concept in the context of AIS brings little novelty to the already saturated field of the immune inspired computational research. This article aims to show that such a component of an AIS has the potential to bring an advantage to a data processing algorithm in terms of data pre-processing, clustering and extraction of features desired by the immune inspired system. The proposed tissue algorithm is based on self-organizing networks, such as self-organizing maps (SOM) developed by Kohonen (1996) and an analogy of the so called Toll-Like Receptors (TLR) affecting the activation function of the clusters developed by the SOM.

Artificial Immune Tissue using Self-Organizing Networks

As introduced by Bentley et al. (2005), artificial immune systems (AIS) are lacking tissue, which is present in one form or another in all living multi-cellular organisms. Some have argued that this concept in the context of AIS brings little novelty to the already saturated field of the immune inspired computational research. This article aims to show that such a component of an AIS has the potential to bring an advantage to a data processing algorithm in terms of data pre-processing, clustering and extraction of features desired by the immune inspired system. The proposed tissue algorithm is based on self-organizing networks, such as self-organizing maps (SOM) developed by Kohonen (1996) and an analogy of the so called Toll-Like Receptors (TLR) affecting the activation function of the clusters developed by the SOM.

Diet, microbes and gut immune responses in the pathogenesis of experimental type 1 diabetes

Type 1diabetes (T1D) is an autoimmune disease, which is influenced by a variety of environmental factors including diet and microbes. These factors affect the homeostasis and the immune system of the gut. This thesis explored the altered regulation of the immune system and the development of diabetes in non-obese diabetic (NOD) mice. Inflammation in the entire intestine of diabetes-prone NOD mice was studied using a novel ex-vivo imaging system of reactive oxygen and nitrogen species (RONS), in relation to two feeding regimens. In parallel, gut barrier integrity and intestinal T-cell activation were assessed. Extra-intestinal manifestations of inflammation and decreased barrier integrity were sought for by studying peritoneal leukocytes. In addition, the role of pectin and xylan as dietary factors involved in diabetes development in NOD mice was explored. NOD mice showed expression of RONS especially in the distal small intestine, which coincided with T-cell activation and increased permeability to macromolecules. The introduction of a casein hydrolysate (hydrolysed milk protein) diet reduced these phenomena, altered the gut microbiota and reduced the incidence of T1D. Extra-intestinally, macrophages appeared in large numbers in the peritoneum of NOD mice after weaning. Peritoneal macrophages (PM) expressed high levels of interleukin-1 receptor associated kinase M (IRAK-M), which was indicative of exposure to ligands of toll-like receptor 4 (TLR-4) such as bacterial lipopolysaccharide (LPS). Intraperitoneal LPS injections activated T cells in the pancreatic lymph nodes (PaLN) and thus, therefore potentially could activate islet-specific T cells. Addition of pectin and xylan to an otherwise diabetes-retarding semisynthetic diet affected microbial colonization of newly-weaned NOD mice, disturbed gut homeostasis and promoted diabetes development. These results help us to understand how diet and microbiota impact the regulation of the gut immune system in a way that might promote T1D in NOD mice.

O papel da lisofosfatidilcolina na ativação do inflamassoma NLRP3 e sua relação com a formação de células gordurosas

Dissertação (mestrado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Molecular, 2016.

Antiviral activity and mechanism of action of arbidol against Hantaan virus infection

Purpose: To investigate the activity and mechanism of action of arbidol against Hantaan virus (HTNV) activity by modulating inflammation via TLR-4 pathway. Methods: HUVEC cells infected with HTNV 76-118 were treated with serially diluted arbidol solutions at -2h (2 h before viral infection, pre-treatment mode), 0 h (at the same time as viral infection, simultaneous treatment mode) or 2 h (2 h after viral infection, post-treatment mode). The transcript levels of TLR4 were detected by semi-quantitative reverse transcription-PCR (RT-PCR) at 6, 12, 18, and 24 h later. The levels of iNOS and TNF-α were examined using enzyme-linked immunosorbent assay (ELISA). Results: Pre-treatment with arbidol, rather than simultaneous treatment or post-treatment, effectively inhibited up-regulation of cellular TLR4 expression (up to 40 ± 6.1 % inhibition) and activity of supernatant iNOS induced by HTNV infection(up to 44.1 ± 9.4 % inhibition), as well as in a LPSstimulated inflammatory endothelial cell. Arbidol decreased the elevated TNF-α levels induced by LPS stimulation. Conclusion: These results are the first evidence that arbidol modulates viral PRRs signaling and its consequential inflammatory cytokine/chemokine response during hantavirus infection.

Anti-inflammatory activity and mechanisms of a lipid extract from hard-shelled mussel (mytilus coruscus) in mice with dextran sulphate sodium-induced colitis

The anti-inflammatory effect of a lipid extract from hard-shelled mussel (HMLE) on dextran sulphate sodium (DSS)-induced colitis in mice was investigated. Salicylazosulphapyridine (SASP) and different doses of HMLE were administered by gastric gavage. HMLE significantly attenuated DSS-induced colitis disease activity index scores, tissue damage, splenic enlargement and colon myeloperoxidase accumulation. In addition, HMLE improved colon oxidative stress and production and expression of anti-inflammatory cytokine, interleukin (IL)-10, while HMLE inhibited the abnormal productions and mRNA expressions of pro-inflammatory cytokines, namely tumour necrosis factor-α, IL-1β, and IL-6, as well as the expression of key molecules in the toll-like receptor (TLR)-4/nuclear factor (NF)-κB signalling pathway. These findings suggest that HMLE has an anti-inflammatory effect on DSS-induced colitis, equivalent to that of SASP, and this effect might be related to the regulation of inflammatory mediators and key molecules in the TLR-4/NF-κB pathway.

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

Background: Preclinical studies have identified certain probiotics as psychobiotics a live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. Objectives: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. An 8 week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1β, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). Results: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. Conclusions: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.