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      Human lung ex vivo infection models

      review-article
      , ,
      Cell and Tissue Research
      Springer Berlin Heidelberg
      Pneumonia, Human lung, Bacteria, Virus, Immunity

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          Abstract

          Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models. The present review gives an overview of common bacterial lung infections, such as pneumococcal infection and of widely neglected pathogens modeled in ex vivo infected lung tissue. The role of ex vivo infected lung tissue for the investigation of emerging viral zoonosis including influenza A virus and Middle East respiratory syndrome coronavirus is discussed. Finally, further directions for the elaboration of such models are revealed. Overall, the introduced models represent meaningful and robust methods to investigate principles of pathogen-host interaction in original human lung tissue.

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          Most cited references102

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          Clinical and economic burden of community-acquired pneumonia among adults in Europe.

          It is difficult to determine the impact of community-acquired pneumonia (CAP) in Europe, because precise data are scarce. Mortality attributable to CAP varies widely between European countries and with the site of patient management. This review analysed the clinical and economic burden, aetiology and resistance patterns of CAP in European adults. All primary articles reporting studies in Europe published from January 1990 to December 2007 addressing the clinical and economic burden of CAP in adults were included. A total of 2606 records were used to identify primary studies. CAP incidence varied by country, age and gender, and was higher in individuals aged ≥65 years and in men. Streptococcus pneumoniae was the most common agent isolated. Mortality varied from <1% to 48% and was associated with advanced age, co-morbid conditions and CAP severity. Antibiotic resistance was seen in all pathogens associated with CAP. There was an increase in antibiotic-resistant strains, but resistance was not related to mortality. CAP was associated with high rates of hospitalisation and length of hospital stay. The review showed that the clinical and economic burden of CAP in Europe is high. CAP has considerable long-term effects on quality of life, and long-term prognosis is worse in patients with pneumococcal pneumonia.
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            Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection

            Summary Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P1 receptor, we elucidate cellular and signaling mechanisms that are important in initiating cytokine storm. Whereas S1P1 receptor is expressed on endothelial cells and lymphocytes within lung tissue, S1P1 agonism suppresses cytokines and innate immune cell recruitment in wild-type and lymphocyte-deficient mice, identifying endothelial cells as central regulators of cytokine storm. Furthermore, our data reveal immune cell infiltration and cytokine production as distinct events that are both orchestrated by endothelial cells. Moreover, we demonstrate that suppression of early innate immune responses through S1P1 signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus. Modulation of endothelium with a specific agonist suggests that diseases in which amplification of cytokine storm is a significant pathological component could be chemically tractable.
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              Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

              Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.
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                Author and article information

                Contributors
                +49 30 450 553137 , stefan.hippenstiel@charite.de
                Journal
                Cell Tissue Res
                Cell Tissue Res
                Cell and Tissue Research
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0302-766X
                1432-0878
                20 December 2016
                2017
                : 367
                : 3
                : 511-524
                Affiliations
                GRID grid.6363.0, ISNI 0000000122184662, Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, , Charité—Universitätsmedizin Berlin, ; Charitéplatz 1, 10117 Berlin, Germany
                Article
                2546
                10.1007/s00441-016-2546-z
                7087833
                27999962
                2fdf1e10-e83a-4499-81e1-e81ff1ee1961
                © Springer-Verlag Berlin Heidelberg 2016

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 3 November 2016
                : 24 November 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Award ID: SFB-TR84, project B6, Z1a, to A.C.H., project B1 t
                Categories
                Review
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2017

                Molecular medicine
                pneumonia,human lung,bacteria,virus,immunity
                Molecular medicine
                pneumonia, human lung, bacteria, virus, immunity

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