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      Once upon a Time

      editorial
      Journal of Innate Immunity
      S. Karger AG

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          Abstract

          Once upon a time there was a world free of a COVID-19 pandemic. Though it is not much more than half a year ago since the first case has been reported, it seems that it will take a very long time until we could live a normal life again. Nothing is like before and also the time after COVID-19 will be dramatically changed. Thus, our pre-COVID-19 world appears to be a fairytale, but now when reaching reality we should be aware that it was only a question of time until a pandemic outbreak would cause collateral damage. Other catastrophes are lining up in waiting loops. For instance, each year more than 35,000 patients die in Europe from infections caused by antibiotic-resistant bacteria. These patients can no longer be saved, since physicians run out of treatment options. Given that these numbers are increasing, one does not have to be a prophet to predict the next global catastrophe. The COVID-19 pandemic must therefore act as a wakeup call. As researchers we have to stop dreaming about fairytales and focus on applied problems that will help to prevent additional life-threatening horror scenarios. The question is not whether the next pandemic will happen, but rather when. In this issue of Journal of Innate Immunity, Sabine Mihm writes about a possible impact of the genetic background in IFNL genes on COVID-19 outcomes [1]. Like many other viruses including the human herpesviruses [2], the oncolytic vesicular stomatitis virus [3], and the human immunodeficiency viruses (HIV) [4], COVID-19 infections trigger massive inflammatory reactions. A better understanding of general principles involved in evoking pathologic inflammatory responses will therefore help to decipher the molecular mechanisms behind the pathology used by the pathogen to cause these severe complications. The respiratory tract is a common port of entry for many viral and bacterial pathogens including COVID-19. Lungs therefore need to be differently protected than other organs. This said, studies focusing on basic pulmonary immune responses will provide important information about the molecular mechanisms which could be used for therapeutic applications [5]. Concerning COVID-19 infections this is of particular importance as patients with underlying diseases such as chronic obstructive pulmonary disease (COPD) are at higher risk to suffer more severe complications. For instance, COPD animal models, as described in the review article by Lloyd Tanner and Andrew Single [6], could be employed for the development of novel COVID-19-relevant models. Though the corona crisis is dominating our daily life at the moment, we cannot entirely change research focus towards COVID-19. All other infectious diseases will remain a threat to public health and need to be investigated. For instance, Han Gao and colleagues show in an elegant study that survivin, a member of the inhibitor of apoptosis family, can impair the apoptotic machinery in CD4+ T cells of patients with ulcerative colitis [7]. In their article, the authors found that survivin can interfere with the expression of FasL, which can be considered an important marker of innate immune responses [8]. Though in a different context, also Anna-Maria Andersson and collaborators investigated the role of apoptotic events, by studying neutrophils, one of the primary effector cells of the innate immune system [9, 10, 11]. In their contribution the authors demonstrated that efferocytosis of apoptotic neutrophils can enhance the ability of Mycobacterium tuberculosis to control HIV-coinfected macrophages. Apoptosis plays also an important role in the article published by Irina Korovina and co-workers [12]. The authors describe that myeloid SOCS3 deficiency can regulate angiogenesis via enhanced apoptotic endothelial cell engulfment. These findings may lead to the development of new antiangiogenic therapies, underlining a strong link between regulation of inflammatory reactions and the induction of sprouting angiogenesis. Insects are an ideal model to study the innate immune system. In the last article published in this issue Gyöngyi Cinege and colleagues carried out functional and developmental analysis of hemocyte subsets and immune compartments. To this end, the authors examined cellular immune responses involving multinucleated giant hemocytes from Zaprionus indianus, an Afrotropical drosophilid species [13]. The authors concluded that the unique features of the cell-mediated immunity of this species provides clues towards the understanding of the immune response accomplished by multinucleated giant hemocytes. Together, we hope that despite the corona crisis we were able to assemble an interesting issue that not only covers COVID-19-related research. Arne Egesten, Lund Heiko Herwald, Lund

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          Most cited references13

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          Neutrophil Extracellular Traps in the Second Decade

          Nearly 15 years after the first description of neutrophil extracellular traps (NETs), our knowledge concerning this structure has expanded considerably. Initially, NETs were considered solely an elaborate function of the innate immune system to combat invading microorganisms. Successively it became clear that NETs have farther-reaching capabilities. They are involved in a series of pathophysiological mechanisms ranging from inflammation to thrombosis where they fulfill essential functions when produced at the right site and the right time but can have a serious impact when generation or clearance of NETs is inadequately controlled. This review provides a concise overview on the far-reaching functions of NETs in health and disease.
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            Neutrophils and Bacterial Immune Evasion

            Neutrophils are an important component of the innate immune system and provide a front line of defense against bacterial infection. Although most bacteria are killed readily by neutrophils, some bacterial pathogens have the capacity to circumvent destruction by these host leukocytes. The ability of bacterial pathogens to avoid killing by neutrophils often involves multiple attributes or characteristics, including the production of virulence molecules. These molecules are diverse in composition and function, and collectively have the potential to alter or inhibit neutrophil recruitment, phagocytosis, bactericidal activity, and/or apoptosis. Here, we review the ability of bacteria to target these processes.
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              Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

              The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.
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                Author and article information

                Journal
                J Innate Immun
                J Innate Immun
                JIN
                Journal of Innate Immunity
                S. Karger AG (Allschwilerstrasse 10, P.O. Box · Postfach · Case postale, CH-4009, Basel, Switzerland · Schweiz · Suisse, Phone: +41 61 306 11 11, Fax: +41 61 306 12 34, karger@karger.com )
                1662-811X
                1662-8128
                May 2020
                15 May 2020
                : 12
                : 3
                : 201-202
                Article
                jin-0012-0201
                10.1159/000508475
                7265726
                32417841
                733bbd65-28da-4731-9e10-db2da6599f61
                Copyright © 2020 by S. Karger AG, Basel

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 6 May 2020
                : 6 May 2020
                : 2020
                Page count
                References: 13, Pages: 2
                Categories
                Editorial

                Immunology
                Immunology

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