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Macrophages were first discovered in 1882 when Elia Metchnikoff recognized them as important phagocytic cells that can engulf any foreign material, including fungal spores. This discovery has proved to be a milestone in establishing the field of innate immunity. Macrophages are still ruling the area after 140 years of their discovery. This book explores the diverse role of macrophages in vertebrate immunity, parasitic, bacterial, and viral infections, regeneration, inflammation, and neurological diseases.

Macrophages --- Activation. --- Research --- Methodology.

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Streptococcus pneumoniae has been for decades the number one bacterial killer of children in the world. Although vaccination with pneumococcal vaccines [PCV7, PCV10, and PCV13 (children) or PPSV23 (adults)] has helped decrease the burden of pneumococcal disease (PD), mortality remains high. Therefore, pathogenesis studies are still key toward our understanding of PD and its control. The introduction of pneumococcal vaccines has also created a niche for vaccine-escape clones. Moreover, the rise of multi-drug resistant clones around the world has also posed a serious threat in recent years. The proposed special issue of Frontiers in Cellular and Infection Microbiology highlights many of the recent advances that have been made in pneumococcal pathogenesis, colonization and antibiotic resistance by groups in Latino America, Europe, and the USA.

pathogenesis --- macrophages --- co-infection --- gene regulation --- biofilm --- drug resistance --- microbial --- Streptococcus pneumoniae

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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.

Dengue viruses. --- Vaccines. --- Monocytes --- NK cells --- Dendritic Cells --- Dengue --- Antibodies --- protection --- Vaccines --- T cells --- Macrophages --- Immunity

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Metabolism --- Glycolysis --- oxidative phosphrylation --- Tumor Microenvironment --- immune cells --- T cells --- Macrophages --- Endothelial Cells

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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.

Dendritic cells --- Macrophages --- Nomenclature. --- nomenclature --- Monocytes --- development --- Dendritic Cells --- Subset --- differentiation --- Antigen Presentation --- Mononuclear Phagocyte System --- Ontogeny