Urokinase receptor-deficient mice mount an innate immune response to and clarify respiratory viruses as efficiently as wild-type mice

Abstract

Keywords: influenza A virus, innate immune response, respiratory syncytial virus, urokinase plasminogen activator receptor (uPAR) Abbreviations: HRSV, human respiratory syncytial virus; uPA, urokinase plasminogen activator; uPAR, urokinase plasminogen activator receptor; DMEM, Dulbeccos Modified Eagles medium; BAL, bronchoalveolar lavage; dpi, days post-infection.The plasminogen activator receptor (uPAR) is required for lung infiltration by innate immune cells in respiratory bacterial infections. In order to verify if this held true for respiratory viruses, wild type (WT) and uPAR knockout (uPAR ¡/¡ ) mice were inoculated intranasally with the human respiratory syncytial virus (HRSV) and the influenza A virus. At several days post-infection (dpi), viral titers in the lungs were determined while cell infiltrates in the bronchoalveolar lavage (BAL) were analyzed by flow cytometry. In the case of influenza A, body weight loss and mortality were also monitored. Only minor differences were observed between infected WT and uPAR ¡/¡ mice, primarily in influenza virus replication and pathology. These results indicate that uPAR does not play a major role in limiting virus replication or in orchestrating the innate immune response against HRSV or influenza infections in mice. This suggests that there are fundamental differences in the immune control of the viral infections studied here and those caused by bacteria.

Protein profiling of nasopharyngeal aspirates of hospitalized and outpatients revealed cytokines associated with severe influenza A(H1N1)pdm09 virus infections: A pilot study

“…We found that the levels of CD14, LPN2, CCL20, CD147, uPAR, EGF, TFF3, MIF were significantly lower, whereas those of RBP4, CXCL5, IL-8, CFD, adiponectin, and CHI3L1 were significantly higher in hospitalized patients. Interestingly, CD14, LCN2, CCL20, uPAR, EGF, MIF, CXCL5, IL-8, adiponectin and CHI3L1 have been already associated with an increased severity of influenza virus infections in mice and humans [26][27][28][29][30][31][32][33][34][35]. By contrast, the present study is the first to demonstrate that increased levels of CD147, RBP4, TFF3, and CFD are associated with hospitalization due to IAV.…”

“…The relative levels of 102 cytokines, chemokines, and growth factors were determined using the Proteome Profiler Human XL Cytokine Array Kit (R&D Systems Inc., USA) according to the manufacturer's instructions. Importantly, this immunoassay was chosen because it includes several biomarkers (e.g., CD14, LCN2, CCL20, uPAR, EGF, MIF, CXCL5, IL-8, adiponectin and CHI3L1), which were previously associated with severe IAV infections [26][27][28][29][30][31][32][33][34][35]. The results were analysed using ImageJ software.…”

Gene expression patterns induced at different stages of rhinovirus infection in human alveolar epithelial cells

“…PLAU/PLAUR system was induced in current study, the finding that is inconsistent with previous reports [ 15 , 17 ]. PLAUR plays a role in infiltration of immune cell is lung bacterial infection although didn’t show similar role in RSV and influenza using murine models [ 56 ]. Coagulation plays an essential role in control and clearance of the infection.…”

Modulation of Cellular Function by the Urokinase Receptor Signalling: A Mechanistic View

“…High SuPAR levels are found not only in the plasma/serum of HIV-infected individuals, but also in the central spinal fluid of patients with neurological complications ( Sidenius et al, 2004 ; Sporer et al, 2005 ; Nebuloni et al, 2009 ). In contrast, only minor differences were observed between wild type and uPAR null mice, infected with the HRSV influenza virus, indicating that the uPAR does not play a major role neither in the modulation of virus replication nor in the innate immune response against influenza infections in vivo ( Ramos et al, 2015 ). The process of virion assembly, budding, and release from the plasma membrane has been very well characterized; it is known that in T lymphocytes the HIV virions budding occurs in lipid rafts whereby host cell cholesterol, sphingolipids, and GPI-linked proteins are incorporated into the viral envelope ( Nguyen and Hildreth 2000 ; Ono and Freed 2001 ).…”