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Inflammation is a fundamental protective mechanism and at the same time the driving force of a variety of major diseases in humans. Indeed, acute self-resolving inflammation usually plays a positive role for the host, as exemplified by infectious diseases where its positive role is well established and testified by its perception as innate immunity. On the other hand, non-resolving inflammation and consequent chronicization is a key determinant of immunopathology and clinical manifestations of most major diseases in humans. As a consequence, it is increasing appreciated that the problem with inflammation is not how often it starts, but how often it fails to resolve. Appropriate resolution of inflammatory responses, which also drives activation of tissue damage repair mechanisms and return of local tissues to homeostasis, is a necessary process for ongoing health. Interestingly, cells sustaining these processes are also key to the proinflammatory responses, and the underlying “pro-resolving” molecular pathways are triggered as part of the pro-inflammatory response. This clearly indicates resolution of inflammation as an active process requiring functional repolarization of inflammatory cells that calls our attention on the underlying molecular mechanisms. The increasing number of anti-inflammatory drugs best-sellers in the pharma market is a clear indication of the relevance of having inflammation under check; nonetheless, there is still a great need for better acting pharmacological tools for the control of inflammation. Indeed, the remarkable success of biological drugs targeting proinflammatory cytokines has indicates that tools able to block proinflammatory mediators have promising applications, but at the same time has made clear that there are intrinsic limitations to this approach which frequently vanish undermine the activity of single targeting drugs, including the well-known redundancy of inflammatory mediators. Under self-limiting conditions inflammation spontaneously resolves in an active process. Some cellular and molecular mechanisms involved in inflammation resolution have been uncovered in the recent past, and include generation of specific cytokines, apoptosis of inflammatory leukocytes, lipid mediators, macrophage repolarization and others are likely to be revealed in the next future, since loss-of-function mutations of an increasing number of genes results in the development of spontaneous inflammation in experimental animals. We argue that “pushing for“ inflammation resolution by exploiting active naturally-occurring pro-resolving processes may have significant advantages over the attempt to simply “push back” inflammation by passive blockade of proinflammatory mediators. At present the research in the field of inflammation aims at identifying and validates new molecules involved in the resolution of inflammation as a basis for the development of innovative therapeutic strategies in chronic inflammatory and autoimmune diseases. This involves the discovery of new natural or synthetic “pro-resolving” molecules from plant and animals and the investigation of endogenous inflammation “pro-resolving” mechanisms, including atypical chemokine receptors, decoy receptors, and microRNA. An extensive effort is focused on the regulation by “pro-resolving” agents on two molecular systems of key relevance in inflammation: the chemokine system, which regulates recruitment, permanence and egress of leukocyte in tissues; and the Toll Like Receptor (TLR)/IL-1R system, which is central for the activation of infiltrating leukocytes.

Regulation of inflammation --- Therapeutic targeting --- Inflammation --- TLR --- Cell migration

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The interplay between host and pathogen is a complex co-evolutionary battle of surveillance and evasion. The pathogen continuously develops mechanisms to subvert the immune response in order to establish infection while the immune system responds with novel mechanisms of detection. Because the majority of Lyme disease pathology is due to an over-exuberant immune response, much research in Borrelia burgdorferi pathogenesis has been devoted to understanding the mammalian host response to the bacterium. Immunological studies continue to be an active area of research employing emerging techniques, such as intra-vital imaging. These studies have furthered our understanding of inflammatory processes during long-term infection and provided some surprising insights, such as the continued presence of bacterial products after clearance. The field of Lyme disease has long debated the etiology of long-term inflammation and recent studies in the murine host have shed light on relevant cell types and inflammatory mediators that participate in the pathology of Lyme arthritis. Live imaging and bioluminescent studies have allowed for a novel view of the bacterial life cycle, including the tick mid-gut, tick-to-mammal transmission and dissemination throughout a mouse. A number of tick and bacterial proteins have been shown to participate in the completion of the enzootic cycle. Novel mechanisms of gene regulation are continuously being identified. However, B. burgdorferi lacks many traditional virulence factors, such as toxins or specialized secretion systems. Many genes in the B. burgdorferi genome have no known homolog in other bacteria. Therefore, studies focusing on host-pathogen interactions have therefore been limited by an incomplete understanding of the repertoire of bacterial virulence factors. Questions such as how the pathogen causes disease, colonizes the tick and evades host immune-surveillance have been difficult to address. Genetic studies involving single gene deletions have identified a number of important bacterial proteins, but a large-scale genomics approach to identify virulence factors has not been attempted until recently. The generation of a site-directed mutagenesis library is an important step towards a detailed analysis of the B. burgdorferi genome and pathogenome. Using this library, high-throughput genomic studies, utilizing techniques such as massively parallel sequencing have been promising and could be used to identify novel virulence determinants of disease in the mammalian host or persistence in the tick vector. Continued research on this unique pathogen and its specific interaction with host and vector may have far reaching consequences and provide insights for diverse disciplines including ecology, infectious disease, and immunology. Here, several reviews will discuss the most recent advances and future studies to be undertaken in the field of B. burgdorferi biology.

Infectious Diseases --- Medicine --- Health & Biological Sciences --- Borrelia burgdorferi --- innate immunity --- adhesins --- Tnseq --- Eicosanoids --- Lyme Disease --- TLR --- c di GMP --- Ixodes scapularis --- Lyme Arthritis

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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

TNFR signaling --- TLR signaling --- NLR Signaling --- cytokine signaling --- antigen receptor signaling --- NF-kB --- Inflammation --- Cancer --- Bone Resorption --- innate and adaptive immunity

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Dual specificity phosphatases (DUSPs) constitute a heterogeneous group of protein tyrosine phosphatases with the ability to dephosphorylate Ser/Thr and Tyr residues from proteins, as well as from other non-proteinaceous substrates including signaling lipids. DUSPs include, among others, MAP kinase (MAPK) phosphatases (MKPs) and small-size atypical DUSPs. MKPs are enzymes specialized in regulating the activity and subcellular location of MAPKs, whereas the function of small-size atypical DUSPs seems to be more diverse. DUSPs have emerged as key players in the regulation of cell growth, differentiation, stress response, and apoptosis. DUSPs regulate essential physiological processes, including immunity, neurobiology and metabolic homeostasis, and have been implicated in tumorigenesis, pathological inflammation and metabolic disorders. Accordingly, alterations in the expression or function of MKPs and small-size atypical DUSPs have consequences essential to human disease, making these enzymes potential biological markers and therapeutic targets. This Special Issue covers recent advances in the molecular mechanisms and biological functions of MKPs and small-size atypical DUSPs, and their relevance in human disease.

hematopoietic cells --- DEPArray --- n/a --- neuroblastoma --- liver steatosis --- MAPK phosphatase --- DUSP-4 --- granule neurons --- neuronal differentiation --- DUSP10 --- cytokines --- MAPKs --- single cell analysis --- macrophage --- asthma --- E. coli infection --- MAPK --- Cpp1 --- nucleotide receptors --- atypical DUSP --- RSV --- Pmp1 --- cannabinoids --- astrocytes --- sepsis --- influenza --- signaling --- triple-negative breast cancer (TNBC) --- differentiation --- HDAC6 (histone deacetylase isoform 6) --- atypical dual-specificity phosphatases --- microtubules --- respiratory viruses --- MK-STYX (MAPK (mitogen-activated protein kinase) phosphoserine/threonine/tyrosine-binding protein) --- dual-specificity phosphatase --- Msg5 --- TLR signaling --- mitogen-activated protein kinase --- fungal MKPs --- macrophages --- MAP Kinase Phosphatase-2 --- inflammation --- Sdp1 --- circulating tumor cells (CTCs) --- MAP kinases --- MAP kinase phosphatases --- P2X7 --- proliferation --- BDNF --- P2Y13 --- T cell --- hypertriglyceridemia --- integrated omics analysis --- post-translational modification --- rhinovirus --- protein stability --- ubiquitination --- dual-specificity phosphatases --- Mkp-1 --- cancer --- brain metastasis --- HER2 --- COPD --- pseudophosphatase

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Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of chronic kidney disease in the sequel. Whereas the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function—in both the short- and long-term—is urgently needed. This Special Issue includes papers investigating the pathological mechanisms of renal inflammation and AKI and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies examining potential new approaches to attenuate kidney dysfunction are included, as well as review articles.

inflammation --- chronic kidney disease --- anemia --- anemia of inflammation --- ESA hyporesponsiveness --- renal tubular epithelial cells --- macrophages --- lipocalin-2 --- iron --- cilastatin --- hypoxia inducible factor-1-α --- ischemia-reperfusion injury --- acute kidney injury --- cyclophilin A --- fibrosis --- renal fibrosis --- tubular necrosis --- preeclampsia --- podocytes --- VEGF --- FSGS --- proteinuria --- endocan --- ESM-1 --- renal replacement therapy --- kidney transplantation --- biomarker --- diabetic nephropathy --- focal segmental glomerulosclerosis --- innate immunity --- membranous nephropathy --- minimal change diseases --- TLR --- NOX1 --- ML171 --- reactive oxygen species --- ERK --- T cells --- glomerulonephritis --- chemokines --- renal disease --- DJ-1 --- ND-13 --- renal inflammation --- oxidative stress --- UUO --- autophagy --- apoptosis --- trehalose --- simvastatin --- endotoxin --- tubular apoptosis --- cytochrome C --- Bcl-XL --- survivin --- hypercholesterolemia --- xanthine oxidase --- NF-κB pathway --- tertiary lymphoid organs --- B cells --- BAFF --- kidney fibrosis --- myofibroblast activation --- extracellular matrix --- Hippo pathway --- verteporfin --- IgAN --- CKD --- progression --- ACEI --- corticosteroids --- costimulation --- coinhibition --- kidney transplant --- SPR --- protein binding affinity --- adaptive immunity --- epithelial-to-mesenchymal transition --- E. cava extracts --- dieckol --- spontaneously hypertensive rats --- angiotensin II --- n/a