Academic literature on the topic 'Inflammatory memory'

Antigen-specific CD8 T cells play a critical role in protecting the host from infection by intracellular pathogens including viruses, bacteria and parasites. During the course of an infection, antigen-specific CD8 T cells undergo proliferative expansion to increase in number, which is followed by contraction and generation of a stable pool of long-lived memory cells. Importantly, memory CD8 T cells provide enhanced resistance to re-infection by the same pathogen. Moreover, the number of memory CD8 T cells correlates strongly with the level of protection against re-infection. Therefore, vaccines designed to promote cellular immunity should logically focus on achieving sufficiently high number of these memory cells for protection. Most current vaccines have relied on inducing antibodies to protect the host by neutralizing pathogens or blocking pathogen entry into the cells. However, there is a recognized need to design vaccines that also stimulate a strong CD8 T cell component of the adaptive immune response in addition to antibodies. Importantly, inflammatory cytokines induced by infection or vaccination with adjuvant act directly or indirectly on CD8 T cells to modulate their expansion, contraction and acquisition of memory characteristics. Thus, an understanding of how inflammatory cytokines regulate CD8 T cell memory differentiation may help guide the strategies for rational vaccine design. My studies examine the roles of inflammatory cytokines in regulating CD8 T cell memory differentiation. Specifically, my studies investigate the timing of inflammatory cytokine exposure and the role of type I IFNs and IL-12 in regulating effector/memory CD8 T cell differentiation, and exploiting the cross-presentation pathway to rapidly generate protective CD8 T cell immunity. Specifically, my results indicate that (i) encounter with inflammatory cytokines during the rapid proliferative phase deflects CD8 T cell differentiation away from memory towards a sustained effector program, (ii) that direct signaling by either type I IFN or IL-12 to the responding CD8 T cells promotes maximal expansion, but neither of these cytokines is essential to regulate the effector/memory differentiation program, and (iii) cross-priming with both cell-associated antigen and antigen-coated, biodegradable microspheres, accelerates CD8 T cell memory development that can be exploited to rapidly generate protective CD8 T cell immunity.

Les cellules souches de la pulpe dentaire humaine (DPSCs) sont des cellules souches mésenchymateuses (MSCs) isolées de la pulpe dentaire. Les DPSCs sont capables de s’auto-renouveler et se différencier en plusieurs types cellulaires tel que les odontoblastes, les ostéoblastes, les chondrocytes, les neuroblastes et les adipocytes. Les propriétés immunitaires des DPSCs sont de plus en plus étudiées, elles hébergent des récepteurs de types Toll à la surface, possedent une activité immuno-modulatrice.Cependant, les propriétés immunitaires comme celles décrites dans les cellules immunitaires professionnelles telles que la phagocytose, la production de composés anti-microbiens et le nouveau concept « Trained immunity » pourraient être étudiées. une brève revue a été élaborée pour mettre en évidence l'ensemble des propriétés immunitaires des DPSCs décrites dans la littérature. Ensuite, expérimentalement, nous avons montré que les DPSCs pouvaient internaliser le pathogène bactérien Bartonella quintana. En outre, nous avons décrit la capacité des DPSCs à développer une immunité entrainée “trained immunity”. Il s’agit d’une mémoire inflammatoire concernant deux cytokines IL-6 et MCP-1. La stimulation des DPSCs avec le ligand bactérien LPS ou PGN induit une augmentation de l’expression et de la production de l'IL-6 et du PGN après un second stimulus. Dans l'ensemble, l'étude des propriétés immunitaires des DPSCs montre que ces dernières peuvent agir comme des cellules immunitaires<br>Dental pulp Stem cells (DPSCs) are mesenchymal stem cells (MSCs) isolated from the dental pulp. DPSCs are able to self-renew and differentiate into several cell types such as odontoblasts, osteoblasts, chondrocytes, neuroblasts and adipocytes.The immune properties of DPSCs are being studied more and more, they harbor Toll-like receptor on the surface and have an immunomodulatory activity.However, immune properties such as those described in professional immune cells such as phagocytosis, production of antimicrobial compounds and the new concept "Trained immunity" could be studied.A brief review has been developed to highlight the set of immune properties of DPSCs described in the literature. Then, experimentally, we showed that DPSCs could internalize the bacterial pathogen Bartonella quintana.In addition, we have described the ability of DPSCs to develop trained immunity. It is an inflammatory memory concerning two cytokines IL-6 and MCP-1. Priming DPSCs with the bacterial ligand LPS or PGN induces an increase in the expression and production of IL-6 and PGN after a second stimulus.Overall, the study of the immune properties of DPSCs shows that DPSCs can act as immune cells

Pharmacology<br>Ph.D.<br>Ischemic stroke is the third leading cause of death and the leading cause of morbidity in the United States. Cognitive deficits, specifically with respect to learning and memory, are a significant contributor to morbidity in stroke patients. Unfortunately, current treatment options must be administered within a thin therapeutic window of the initial infarct. This requirement results in less than 10% of stroke patients being eligible for treatment. There are currently no treatment options that are effective in the subacute phase of the disease and no treatments that are effective in reversing postischemic learning and memory deficits. We sought to examine the potential efficacy of the anti-inflammatory Cannabinoid-2 Receptor Agonist, O-1966, in attenuating infarct expansion and reversing cognitive deficits in the subacute phase of the disease using a photothrombosis model of stroke. Additionally, we sought to characterize the inflammatory response in photothrombosis. Mice were treated with repeated doses of O-1966 or vehicle and were sacrificed at 24 hours and 7 days to study the acute and subacute phase of the disease respectively. Learning and memory testing, immunohistochemistry, and polymerase chain reaction were used to measure the effect of O-1966 on infarct expansion, inflammatory gene expression, and cognitive function. In addition to PCR, flow cytometry was used to characterize the temporal dynamics of inflammation following photothrombosis. Our studies show that O-1966 is effective in the subacute phase in attenuating infarct expansion and proinflammatory gene expression and reversing learning and memory deficits.<br>Temple University--Theses

Thesis (Ph. D.)--Georgia State University, 2007.<br>Title from title page. Lindsey L. Cohen, committee chair; Lisa Armistead, Erin B. McClure, Mary K. Morris, committee members. Electronic text (113 p. : ill. (some col.)) : digital, PDF file. Description based on contents viewed Oct. 11, 2007. Includes bibliographical references (p. 73-80).

Inflammatory bowel disease (IBD; Crohn’s disease & ulcerative colitis) is a chronic illness in which medication and dietary adherence may determine disease natural history and severity of symptoms. We hypothesized that age, prospective memory (PM) and body satisfaction would predict medication and dietary adherence in adolescents with IBD and that gender and age would modify the relation between body satisfaction and adherence, with older girls being less adherent than younger children. Fifty-seven participants aged 10-21 (M = 16.5, SD = 2.3) with IBD and their caregivers were recruited. Informed consent, demographics and body satisfaction questionnaires were completed. PM was assessed using a naturalistic task. Adherence was measured by the 1-week completion of a medication and dietary log. A questionnaire was administered to evaluate coping strategies used for overcoming obstacles to dietary adherence. Two hierarchical regressions were conducted for medication and diet adherence respectively. As hypothesized, age had a significant effect (â = -.42, p < .01) on dietary adherence, accounting for approximately 17% of the variance (R2change = .17; Fchange (1,41) = 8.57, p = .006), with younger children being more adherent. Body satisfaction had a greater and more significant effect on dietary adherence than age (â = -.33, p < .01); i.e. participants more satisfied with their body reported better dietary adherence (R2change = .28; Fchange (2,35) = 6.97, p < .05). Findings remained consistent across multiple measures of body satisfaction and dietary adherence. None of the predictors had a significant effect on medication adherence. Health care providers who treat adolescents with IBD and parents should be made aware of factors affecting adherence in order to improve disease outcomes and patients’ quality of life.

A hipermetioninemia é uma condição caracterizada por altos níveis de metionina no sangue e em outros tecidos, podendo causar danos neurológicos, hepáticos e musculares. Considerando que a placenta transfere a metionina do sangue materno para a circulação fetal e que pouco se sabe sobre o efeito da hipermetioninemia gestacional sobre o feto em desenvolvimento, o principal objetivo deste trabalho foi desenvolver um modelo animal de hipermetioninemia materna quimicamente induzido em ratas e utilizar o mesmo para investigar parâmetros bioquímicos (estresse oxidativo, atividade da Mg2+-ATPase, atividade e imunoconteúdo da Na+,K+-ATPase, número de neurônios, níveis de neurotrofinas, metabolismo energético, inflamação e apoptose), moleculares (expressão gênica da Na+,K+-ATPase) e histológicos (microscopia eletrônica) nos encéfalos da prole, bem como avaliar tarefas comportamentais (campo aberto, esquiva inibitória e reconhecimento de objetos). Também analisamos parâmetros de estresse oxidativo/nitrosativo no músculo esquelético e parâmetros de dano muscular e inflamação no soro da prole. A hipermetioninemia foi induzida em ratas através de duas injeções subcutâneas diárias de metionina durante todo o período gestacional. Um grupo de ratas recebeu a dose 1 (1,34 μmol/g peso corporal) e outro recebeu a dose 2 (2,68 μmol/g peso corporal). O grupo controle recebeu salina. Após o nascimento, um grupo de filhotes foi eutanasiado no sétimo dia de vida e outro grupo foi eutanasiado aos 21 dias. Ambas as doses aumentaram os níveis encefálicos de metionina das mães e a dose 2 aumentou os níveis de metionina nos encéfalos da prole. Após estabelecer o modelo, a dose 2 de metionina foi escolhida para estudar os efeitos do tratamento sobre a prole. Os testes bioquímicos subsequentes foram realizados nos filhotes de 21 dias, a histologia foi realizada na prole de 21 e 30 dias e os testes comportamentais foram realizados em filhotes de 30 dias. Os resultados demonstraram que a hipermetioninemia materna reduziu a atividade da Na+,K+-ATPase, Mg2+- ATPase, catalase e complexo II/succinato desidrogenase, o conteúdo de sulfidrilas, número de neurônios e níveis de NGF e BDNF, bem como aumentou os níveis de RNAm e imunoconteúdo da Na+,K+-ATPase nos encéfalos dos filhotes. Foram observados também alterações morfológicas, indicativas de degeneração celular nos neurônios da prole, e os testes comportamentais indicaram deficit de memória. Com relação aos danos musculares, houve um aumento na produção de espécies reativas de oxigênio e lipoperoxidação e uma redução do conteúdo de sulfidrilas, atividades das enzimas antioxidantes e nos níveis de nitritos no músculo esquelético da prole. A atividade da creatina cinase foi reduzida e os níveis de ureia e proteína C reativa foram aumentados no soro. Esses resultados foram acompanhados por perda de massa muscular. Tais achados mostraram que a hipermetioninemia gestacional induziu alterações bioquímicas, moleculares e histológicas no encéfalo e bioquímicas no músculo esquelético e soro dos filhotes, as quais podem contribuir para o entendimento dos mecanismos fisiopatológicos envolvidos nos danos neurológicos e musculares causados por essa condição. Ressaltamos a importância do desenvolvimento do referido modelo de hipermetioninemia gestacional que além de ampliar o entendimento da toxicidade de altos níveis metionina, também abriu perspectivas para novos estudos a respeito dos efeitos ocasionados pela exposição ao excesso de metionina devido a uma condição genética ou uma dieta rica em proteína durante a vida pré-natal.<br>Hypermethioninemia is a condition characterized by elevated levels of methionine in blood and other tissues and may cause neurological, hepatic and muscular damages. Considering that placenta transfers methionine from maternal blood to the fetal circulation and little is known about the effect of gestational hypermetioninemia on the developing fetus, the main objective of this work was to develop a chemically induced animal model of maternal hypermethioninemia in rats and to use it to investigate biochemical (oxidative stress, activity of Mg2+-ATPase, activity and immunocontent of Na+,K+-ATPase, number of neurons, neurotrophins levels, energy metabolism, inflammation, and apoptosis), molecular (gene expression of Na+,K+-ATPase) and histological parameters (electron microscopy) in encephalon of the offspring, as well as evaluate behavioral tasks (open field, inhibitory avoidance and object recognition). We also analyzed oxidative/nitrosative stress parameters in skeletal muscle and parameters of muscle damage and inflammation in serum of the offspring. Hypermethioninemia was induced in rats through two daily subcutaneous injections of methionine throughout the gestational period. A group of pregnant rats received dose 1 (1.34 μmol/g body weight) and the other received dose 2 (2.68 μmol/g body weight). The control group received saline. After birth, a first group of pups was euthanized at the 7th day of life and the second group at the 21st day of life. Both doses 1 and 2 increased methionine levels in the brain of the mother rats and dose 2 increased methionine levels in encephalon of the offspring. After establishing the experimental model, the highest dose of methionine was chosen to study the effects of treatment on offspring. The subsequent biochemical tests were performed on 21-day-old pups, histological analyses were performed on offspring of 21 and 30 days of age, and behavioral tests were performed on 30-day-old pups. The results demonstrated that maternal hypermethioninemia reduced Na+,K+-ATPase, Mg2+-ATPase, catalase and complex II/succinate dehydrogenase activities, sulfhydryl content, number of neurons and levels of NGF and BDNF, as well as increased levels of mRNA and immunocontent of Na+,K+-ATPase in the brains of the pups. Morphological changes indicative of cellular degeneration were also observed in offspring neurons, and behavioral tests indicated memory deficit. With regard to muscle damage, there was an increase in the production of reactive oxygen species and lipoperoxidation, and a reduction of the sulfhydryl content, antioxidant enzymes activities and in the levels of nitrites in skeletal muscle of the offspring. Creatine kinase activity was reduced and urea and C-reactive protein levels were increased in serum. These results were accompanied by loss of muscle mass. These findings showed that gestational hypermethioninemia induced biochemical, molecular and histological changes in the brain and biochemical changes in skeletal muscle and serum of pups, which may contribute to the understanding of the pathophysiological mechanisms involved in the neurological and muscular damages caused by this condition. We emphasize the importance of the development of this model of gestational hypermetioninemia that, in addition to increasing the understanding of toxicity of high methionine levels, also opened perspectives for new studies regarding the effects caused by exposure to excess methionine due to a genetic condition or a diet rich in protein during prenatal life.

CD8 T cells are essential for the elimination of intracellular pathogens and tumor cells. Understanding how naïve CD8 T cells differentiate into effector cells capable of eliminating pathogens and to generate adequate memory cells during immune responses is fundamental for optimal T cell vaccine design. In this PhD thesis work we addressed two central questions: 1) What are the mechanisms by which early effector T cells could act as pro-inflammatory effectors? And what is their role in the immune response? 2) How heterogeneous are CD8 responses? Could different pathogens modulate CD8 T cell differentiation programs and be responsible for CD8 cell-to-cell heterogeneity? Could they also generate memory cells with different protection capacities? To address these questions related to the diversity of CD8 T cell differentiation during immune responses, we used the single cell RT-PCR technique to detect ex vivo expression of mRNA in each individual cell, and Brefeldin A injected mice to detect ex vivo intracellular proteins. As experimental system to evaluate in vivo cell activation we used T cell receptor transgenic (TCR-Tg) CD8 T cells. Since the use of TCR-Tg cells to study immune responses has been subjected to criticism (due to high frequency of naïve-precursor transfers), in a first Ms. we compared the behavior of TCR-Tg and endogenous (non-transgenic and present at low frequency) cells in the same mouse. We found fully overlapping behavior between these two cell populations, which reinforced the advantage of using TCR-Tg cells to study CD8 immune responses. In addition, we concluded that the frequency of naïve-precursors do not induce diversity on CD8 T cell differentiation patterns. In a second Ms. we evaluated the impact of different pathogens in the diversity of CD8 T cell properties during two different immune responses: OT1 TCR-Tg cells (specific for OVA antigen) in the response to LM-OVA (Listeria Monocytogenes expressing OVA) infection; and P14 TCR-Tg cells (specific for GP33 epitope) in the response to Lymphocytic choriomeningitis vírus (LCMV) infection. We found that OT1 and P14 cells had different properties. As this difference could also be attributed to the different TCR avidity between OT1 and P14 cells, we then compared the behavior of P14 and OT-1 cells in the same mouse, co-injected with LM-OVA and LM-GP33. Since no differences were then detected, these results demonstrated that priming with different pathogens generates CD8 T cells with different characteristics that are not determined by TCR usage, but rather by the infection context. In addition, when looking for the protection capacity of endogenous CD8 memory cells generated in bacterial or viral context, we found that memory cells generated after LCMV priming were more efficient in responding to a second challenge, than memory cells generated after LM-GP33 priming. We also found that this better protection is associated with a T cell effector memory (TEM) phenotype associated with the LCMV infection, in contrast with a T cell central memory (TCM) phenotype generated after LM-OVA infection. These results demonstrate that different pathogens are responsible for diversity of CD8 T cell differentiation patterns and that even when distinct pathogens are efficiently eliminated during the primary immune response the quality of the memory generated may differ. In a third Ms. we studied the mechanisms by which effector CD8 T cells attracted other cell types in the early days of an immune response. We used two experimental systems: the response of OT1 TCR-Tg cells to LM-OVA infection; and the response of anti-HY TCR-Tg cells to male cells ("sterile"-non infectious context). In both cases we found that immediately after activation, CD8 T cells expressed high levels of pro-inflammatory cytokines and chemokines (such as TNFα, XCL1, CCL3 and CCL4). (...)