Project description:The aim of the study is to evaluate whether the preoperative level of myeloid-derived suppressor cells is associated with postoperative complications classified by Clavien-Dindo categories. Levels of all MDSC, polymorphonuclear MDSC (PMNMDSC), monocytic MDSC (MMDSC), early-stage MDSC (EMDSC) and monocytic to polymorphonuclear MDSC ratio (M/PMN MDCS) were established and compared in patients with postoperative complications, severe postoperative complications (>= IIIA according to Clavien-Dindo) and severe septic complications.
Project description:Influenza A virus (IAV) infection causes an acute respiratory disease characterized by a strong inflammatory immune response and severe immunopathology. Pro-inflammatory mechanisms are well described in the murine IAV infection model, but less is known about the mechanisms leading to the resolution of inflammation. Here, we analyzed the contribution of monocytic myeloid-derived suppressor cells (mono-MDSC) to this process. An accumulation of mono-MDSC within the lungs was observed during the course of IAV infection and phenotypic characterization of these mono-MDSC by flow cytometry and RNA-Seq revealed an activated phenotype showing both pro- and anti-inflammatory features, including the expression of iNOS by a fraction of cells in an IFN-g-dependent manner. Mono-MDSC isolated from lungs of IAV-infected animals displayed suppressive activity when tested in vitro, and iNOS inhibitors could abrogate this suppressive activity. Collectively, our data suggest that during IAV infection monocytes can differentiate into mono-MDSC, which might contribute to the prevention of immunopathology during this life-threatening disease.
Project description:Mice were infected intranasally with 1.5x10E5 PFU and total RNA were extracted from mice lungs at day 3. RNA samples were extracted from mice lung infected or not by influenza virus.
Project description:The pathogenesis of avian influenza A H5N1 virus in human has not been clearly elucidated. There have been increasing evidence suggesting a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. However, the role of aberrant innate immune response in human lungs infected by avian influenza H5N1 virus has not been explored and direct evidence for inappropriate innate responses in lungs of avian influenza H5N1 virus infected patients is lacking.
Project description:To further understand the molecular pathogenesis of the 2009 pandemic H1N1 influenza virus infection, we profiled cellular miRNAs of lung tissue from BALB/c mice infected with influenza virus BJ501 and a mouse-adapted influenza virus A/Puerto Rico/8/34 (H1N1)(PR8) as a comparison. Five groups of mice were selected, and three of each group were used to profile the miRNA, two were in case for unqualified RNA extraction. Whole lungs from mice infected by BJ501 or PR8 were harvested on 2,5 days post infection (dpi), and compared with lung samples from 5 uninfected mice.
Project description:Metabolomics analysis of C57BL/6 mouse lungs infected with influenza A/California/04/09 (H1N1) virus, mock infected with PBS, or untreated.
Project description:Metabolomics analysis of C57BL/6 mouse lungs infected with influenza A/Vietnam/1203/04 (H5N1) HALo virus, mock infected with PBS, or untreated.
Project description:The pathogenesis of avian influenza A H5N1 virus in human has not been clearly elucidated. There have been increasing evidence suggesting a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. However, the role of aberrant innate immune response in human lungs infected by avian influenza H5N1 virus has not been explored and direct evidence for inappropriate innate responses in lungs of avian influenza H5N1 virus infected patients is lacking. In order to obtain evidences for the proposed role of aberrant innate immune response in avian influenza H5N1 virus pathogenesis in human, we analyzed expression profile of lung tissues from two fatal cases of avian influenza H5N1 virus infected patients in comparison to normal human lung using an expression microarray.
Project description:During influenza pneumonia, the alveolar epithelial cells of the lungs are targeted by influenza virus. The distal airway stem cells (DASCs) and proliferating alveolar type II (AT2) cells are reported to be putative lung repair cells. However, their relative spatial and temporal distribution is still unknown during influenza-induced acute lung injury. Here, we investigated the distribution of these cells, and concurrently performed global proteomic analysis of the infected lungs to elucidate and link the cellular and molecular events during influenza pneumonia recovery. BALB/c mice were infected with a sub-lethal dose of influenza H1N1 virus. From 5 to 25 days post-infection (dpi), mouse lungs were subjected to histopathologic and immunofluorescence analysis to probe for global distribution of lung repair cells (using P63 and KRT5 markers for DASCs; PCNA and SPC markers for AT2 cells). At 7 and 15 dpi, infected mouse lungs were also subjected to protein mass spectrometry for relative protein quantification. DASCs appeared only in the damaged area of the lung from 7 dpi onwards, reaching a peak at 21 dpi, and persisted at 25 dpi. However, no differentiation of DASCs to AT2 cells was observed by 25 dpi. In contrast, AT2 cells began proliferating from 7 dpi to replenish its population. Mass spectrometry and gene ontology analysis revealed prominent innate immune response at 7 dpi, which shifted towards adaptive immune responses by 15 dpi. Hence, proliferating AT2 cells but not DASCs contribute to AT2 cell regeneration following transition from innate to adaptive immune responses during the early phase of recovery from influenza pneumonia up to 25 dpi.