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Protective Immune Response to Dengue Virus Infection and Vaccines: perspectives from the field to the bench

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195114 Year: Pages: 97 DOI: 10.3389/978-2-88919-511-4 Language: English
Publisher: Frontiers Media SA
Subject: Allergy and Immunology --- Medicine (General)
Added to DOAB on : 2015-12-03 13:02:24
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Abstract

Dengue is the most important mosquito-transmitted viral disease in humans. Half of the world population is at risk of infection, mostly in tropical and sub-tropical areas. The World Health Organization (WHO) estimates that 50 to 100 million infections occur yearly, with 50,000 to 100,000 deaths related to dengue, mainly in children. Recent estimates show higher numbers, up to three times more, with 390 million estimated dengue infections per year, among which 96 million apparent infections (Bhatt et al. 2013). Initially localized to South-East Asia, dengue virus (DENV) started its spread in Latin America in the 80s. Little is known about DENV spread in Africa, but multiple seroprevalence surveys over several years are now clearly showing endemic areas in East and West Africa (Brady et al. 2013). Finally, due to global warming and intense traveling there is a risk of global spread towards more temperate regions, and both US Key islands (FL) and southern Europe recently faced DENV outbreaks. There are currently no specific treatments or vaccines available. Even though several dengue vaccines are in the pipeline, clear correlates of protection are still lacking. The recent failure of the live-attenuated Sanofi vaccine Phase 2b trial (Sabchareon et al. 2013) and the lack of correlation between clinical protection and in vitro neutralization assays, clearly underlines the necessity to better understand the role of the different components of the immune system in protection against dengue virus infection and the requirement for the development of additional and/or improved predictive assays. The aim of this research topic is to provide novel data, opinions and literature reviews on the best immune correlates of protection and recent advances in the immune response to DENV infection that can allow rapid progress of dengue vaccines. Authors can choose to submit original research papers, reviews or opinions on pre-clinical or clinical observations that will help unify the field, with perspectives from epidemiology, virology, immunology and vaccine developers. This research topic will discuss different aspects of the protective immune response to DENV that can influence vaccine development. It will include a review of epidemiological data generated in the field, which will address spatio-temporal diversity of DENV epidemics, the importance of cross-reactive protection and of the time-interval between infections as a predictor of disease. It will further include a review of the role of both the innate and adaptive immunity in DENV infection control, and discuss the usefulness of new improved animal models in dissecting the role of each immunological compartment, which will help define new correlate of immune protection. New data concerning the DENV structure and anti-dengue antibody structure will address the necessity of improved neutralization assays. The ultimate test to prove vaccine efficacy and study immune correlates of protection in humans before large trials will open up the discussion on human DENV challenges using controlled attenuated viral strains. Finally, the role of vaccines, administered in flavi-immune populations, in the modification of future epidemics will also be approached and will include novel studies on mosquitoes infection thresholds.

Dendritic Cell and Macrophage Nomenclature and Classification

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889199181 Year: Pages: 202 DOI: 10.3389/978-2-88919-918-1 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Allergy and Immunology
Added to DOAB on : 2016-01-19 14:05:46
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The mononuclear phagocyte system (MPS) comprises dendritic cells (DCs), monocytes and macrophages (MØs) that together play crucial roles in tissue immunity and homeostasis, but also contribute to a broad spectrum of pathologies. They are thus attractive therapeutic targets for immune therapy. However, the distinction between DCs, monocytes and MØ subpopulations has been a matter of controversy and the current nomenclature has been a confounding factor. DCs are remarkably heterogeneous and consist of multiple subsets traditionally defined by their expression of various surface markers. While markers are important to define various populations of the MPS, they do not specifically define the intrinsic nature of a cell population and do not always segregate a bona fide cell type of relative homogeneity. Markers are redundant, or simply define distinct activation states within one subset rather than independent subpopulations. One example are the steady-state CD11b+ DCs which are often not distinguished from monocytes, monocyte-derived cells, and macrophages due to their overlapping phenotype. Lastly, monocyte fate during inflammation results in cells bearing the phenotypic and functional features of both DCs and MØs significantly adding to the confusion. In fact, depending on the context of the study and the focus of the laboratory, a monocyte-derived cell will be either be called "monocyte-derived DCs" or "macrophages". Because the names we give to cells are often associated with a functional connotation, this is much more than simple semantics. The "name" we give to a population fundamentally changes the perception of its biology and can impact on research design and interpretation. Recent evidence in the ontogeny and transcriptional regulation of DCs and MØs, combined with the identification of DC- and MØ-specific markers has dramatically changed our understanding of their interrelationship in the steady state and inflammation. In steady state, DCs are constantly replaced by circulating blood precursors that arise from committed progenitors in the bone marrow. Similarly, some MØ populations are also constantly replaced by circulating blood monocytes. However, others tissue MØs are derived from embryonic precursors, are seeded before birth and maintain themselves in adults by self-renewal. In inflammation, such differentiation pathways are fundamentally changed and unique monocyte-derived inflammatory cells are generated. Current DC, monocyte and MØ nomenclature does not take into account these new developments and as a consequence is quite confusing. We believe that the field is in need of a fresh view on this topic as well as an upfront debate on DC and MØ nomenclature. Our aim is to bring expert junior and senior scientists to revisit this topic in light of these recent developments. This Research Topic will cover all aspects of DC, monocyte and MØ biology including development, transcriptional regulation, functional specializations, in lymphoid and non-lymphoid tissues, and in both human and mouse models. Given the central position of DCs, monocytes and MØs in tissue homeostasis, immunity and disease, this topic should be of interest to a large spectrum of the biomedical community.

Second hand smoke and COPD: lessons from animal studies

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193165 Year: Pages: 91 DOI: 10.3389/978-2-88919-316-5 Language: English
Publisher: Frontiers Media SA
Subject: Physiology --- Science (General)
Added to DOAB on : 2016-02-05 17:24:33
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Cigarette smoke exposure is the key initiator of chronic inflammation, alveolar destruction, and the loss of alveolar blood vessels that lead to the development of chronic obstructive pulmonary disease (COPD) which is comprised of emphysema and chronic bronchitis. Exposure to secondhand smoke (SHS) is the major risk factor for non-smokers to develop emphysema. While the first-hand smoke is directly inhaled by smokers, passive smoking occurs when non-smokers are involuntary exposed to environmental tobacco smoke also known as second hand smoke (SHS). SHS is a mixture of 2 forms of smoke that come from burning tobacco: side stream smoke (smoke that comes from the end of a lit cigarette, pipe, or cigar) and mainstream smoke (smoke that is exhaled by a smoker). These two types of smoke have basically the same composition, however in SHS many toxic components are more concentrated than in first-hand smoke, therefore more hazardous for people’s health. Several pathological events have been implicated in the development of SHS-induced COPD, but many aspects of this pathology remain poorly understood halting the development of new advanced treatments for this detrimental disease. In this respect we have welcomed leading investigators in the field to share their research findings and provide their thoughts regarding the mechanisms of the SHS exposure-induced immune responses and inflammatory mechanisms of lung destruction in SHS-induced COPD and related comorbidities.

AMP-Activated Protein Kinase Signalling

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ISBN: 9783038976622 Year: Pages: 452 DOI: 10.3390/books978-3-03897-663-9 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-03-21 14:08:22
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Starting from a kinase of interest, AMP-activated protein kinase (AMPK) has gone far beyond an average biomolecule. Being expressed in all mammalian cell types and probably having a counterpart in every eukaryotic cell, AMPK has attracted interest in virtually all areas of biological research. Structural and biophysical insights have greatly contributed to a molecular understanding of this kinase. From good old protein biochemistry to modern approaches, such as systems biology and advanced microscopy, all disciplines have provided important information. Thus, multiple links to cellular events and subcellular localizations have been established. Moreover, the crucial involvement of AMPK in human health and disease has been evidenced. AMPK accordingly has moved from an interesting enzyme to a pharmacological target. However, despite our extensive current knowledge about AMPK, the growing community is busier than ever. This book provides a snapshot of recent and current AMPK research with an emphasis on work providing molecular insight, including but not limited to novel physiological and pathological functions, or regulatory mechanisms. Up-to-date reviews and research articles are included.

Keywords

exercise --- glucose uptake --- AMP-activated protein kinase --- TBC1D4 --- AS160 --- AMP-activated protein kinase --- developmental origins of health and disease (DOHaD) --- hypertension --- kidney disease --- nutrient-sensing signals --- oxidative stress --- renin-angiotensin system --- AMPK --- autophagy --- co-expression --- microarrays --- 3T3-L1 --- adipocyte --- differentiation --- AMPK --- tight junctions --- epithelial cells --- ZO-1 --- par complex --- MDCK --- nectin-afadin --- adherent junctions --- TAK1 --- AMPK --- phosphorylation --- AMPK kinase --- endothelial nitric-oxide synthase --- vasodilation --- phenylephrine --- vasoconstriction --- endothelial cells --- ionomycin --- AMPK --- liver --- lipid metabolism --- fatty acid oxidation --- indirect calorimetry --- atrophy --- regrowth --- sirtuin 1 (SIRT1) --- peroxisome proliferator-activated receptor gamma coactivator 1-? (PGC1?) --- heat shock protein --- fiber-type --- AMPK --- monocytes --- macrophages --- differentiation --- autophagy --- AML --- MDS --- CML --- CMML --- pregnancy --- catechol-O-methyltransferase --- 2-methoxyestradiol --- preeclampsia --- gestational diabetes mellitus --- AMPK --- IL-1? --- NLRP3 --- nutrition --- dietary fatty acids --- metabolic-inflammation --- nutrigenomics --- AMPK --- LKB1 --- autophagy --- proteasome --- hypertrophy --- atrophy --- skeletal muscle --- AICAR --- mTOR --- protein synthesis --- AMPK --- epigenetics --- chromatin remodeling --- histone modification --- DNA methylation --- medulloblastoma --- sonic hedgehog --- AMPK --- AMP-activated protein kinase (AMPK) --- spermatozoa --- motility --- mitochondria --- membranes --- signaling --- stress --- assisted reproduction techniques --- AMP-activated protein kinase --- epigenetics --- protein acetylation --- KATs --- HDACs --- acetyl-CoA --- NAD+ --- AMP-activated protein kinase --- glycogen --- exercise --- metabolism --- cellular energy sensing --- energy utilization --- liver --- skeletal muscle --- metabolic disease --- glycogen storage disease --- resveratrol --- AMPK --- hepatocyte --- liver --- steatosis --- transporter --- carrier --- pump --- membrane --- energy deficiency --- AMPK --- infection --- mycobacteria --- host defense --- energy metabolism --- AMPK --- activation loop --- AID --- ?-linker --- ?-linker --- CBS --- LKB1 --- CaMKK2 --- ?RIM --- hypothalamus --- adenosine monophosphate-activated protein kinase --- adipose tissue --- food intake --- adaptive thermogenesis --- beiging --- AMPK --- HDAC4/5 --- p70S6K --- MyHC I(?), motor endplate remodeling --- soleus muscle --- mechanical unloading --- hindlimb suspension --- AMPK --- synaptic activation --- PKA --- CREB --- soluble Adenylyl cyclase --- Immediate early genes --- transcription --- AMPK --- autophagy --- metabolism --- mTOR --- ULK --- AMP-activated protein kinase --- protein kinase B --- Akt --- insulin signalling --- A769662 --- endothelial function --- n/a

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