Frontiers in immunology
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Frontiers in immunology · Jan 2019
Multicenter Study Clinical TrialTraumatic Injury and Exposure to Mitochondrial-Derived Damage Associated Molecular Patterns Suppresses Neutrophil Extracellular Trap Formation.
Major traumatic injury induces significant remodeling of the circulating neutrophil pool and loss of bactericidal function. Although a well-described phenomenon, research to date has only analyzed blood samples acquired post-hospital admission, and the mechanisms that initiate compromised neutrophil function post-injury are therefore poorly understood. Here, we analyzed pre-hospital blood samples acquired from 62 adult trauma patients (mean age 44 years, range 19-95 years) within 1 h of injury (mean time to sample 39 min, range 13-59 min). ⋯ Indeed, activation of AMPK via treatment with the AMP-mimetic AICAR significantly reduced neutrophil lactate production in response to PMA stimulation, a phenomenon that we also observed for neutrophils pre-treated with mtDAMPs. Furthermore, the impairment in NET generation induced by mtDAMPs was partially ameliorated by pre-treating neutrophils with the AMPK inhibitor compound C. Taken together, our data demonstrate an immediate trauma-induced impairment in neutrophil anti-microbial function and identify mtDAMP release as a potential initiator of acute post-injury neutrophil dysfunction.
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Frontiers in immunology · Jan 2019
ReviewSerological Diagnosis of Autoimmune Bullous Skin Diseases.
Autoimmune bullous dermatoses (AIBD) encompass a variety of organ-specific autoimmune diseases that manifest with cutaneous and/or mucosal blisters and erosions. They are characterized by autoantibodies targeting structural proteins of the skin, which are responsible for the intercellular contact between epidermal keratinocytes and for adhesion of the basal keratinocytes to the dermis. The autoantibodies disrupt the adhesive functions, leading to splitting and blister formation. ⋯ The identification of various target antigens has paved the way for the recent development of numerous specific autoantibody tests. In particular, optimized designer antigens and multiplex test formats for indirect immunofluorescence and ELISA have enhanced and refined the laboratory analysis, enabling highly efficient serodiagnosis and follow-up. This review elaborates on the current standards in the serological diagnostics for autoimmune bullous dermatoses.
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Frontiers in immunology · Jan 2019
ReviewCan Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
The unprecedented clinical activity of checkpoint blockade in several types of cancers has formally demonstrated that anti-tumor immune responses are crucial in cancer therapy. Durable responses seen in patients treated with immune checkpoint inhibitors (ICI) show that they can trigger the establishment of long-lasting immunologic memory. This beneficial outcome is however achieved for a limited number of patients. ⋯ How can this be prevented through combination therapies? We here review the functions of immune checkpoints, the successes of ICI in treating cancer and their therapeutic limits. We discuss how conventional cancer therapies can be properly selected to set up combinatorial approaches with ICI leading to treatment improvement. We finally summarize clinical data showing the ongoing progress in cancer treatment involving ICI and chemotherapy combination strategies.
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Frontiers in immunology · Jan 2019
ReviewImpact of Obesity on Influenza A Virus Pathogenesis, Immune Response, and Evolution.
With the rising prevalence of obesity has come an increasing awareness of its impact on communicable disease. As a consequence of the 2009 H1N1 influenza A virus pandemic, obesity was identified for the first time as a risk factor for increased disease severity and mortality in infected individuals. Over-nutrition that results in obesity causes a chronic state of meta-inflammation with systemic implications for immunity. ⋯ Finally, we summarized the effectiveness of current vaccines and antivirals in this populations and the questions that remain to be answered. If current trends continue, nearly 50% of the worldwide population is projected to be obese by 2050. This population will have a growing impact on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus.
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Frontiers in immunology · Jan 2019
Lytic Susceptibility, Structure, and Mechanical Properties of Fibrin in Systemic Lupus Erythematosus.
Among complications of systemic lupus erythematosus (SLE), thrombotic events are relatively common and contribute significantly to the morbidity and mortality rates. An increased risk of thrombosis in various diseases has been shown to be associated with the lytic stability and mechanical stiffness of the fibrin clot determined by its structure. Here we studied alterations of the fibrin clot properties in relation to disease severity in SLE patients. ⋯ In conclusion, changes in the blood composition associated with active systemic inflammation in SLE cause significant alterations in the lytic resistance of fibrin clots associated with changes in polymerization kinetics, viscoelastic properties, and structure. The formation of more rigid prothrombotic fibrin clots in the plasma of SLE patients is likely due to the inflammatory hyperfibrinogenemia and greater extent of crosslinking. However, the higher susceptibility of the SLE clots to fibrinolysis may be a protective and/or compensatory mechanism that reduces the risk of thrombotic complications and improves patient outcomes.