http://hdl.handle.net/10033/6816 AG Infektionsimmunologie (INI) Sun, 19 May 2013 20:44:54 GMT 2013-05-19T20:44:54Z http://hdl.handle.net/10033/269032 Title: The expanding world of extracellular traps: not only neutrophils but much more. Authors: Goldmann, Oliver; Medina, Eva Abstract: The release of extracellular traps (ETs) is a recently described mechanism of innate immune response to infection. Although ETs have been intensely investigated in the context of neutrophil antimicrobial effector mechanisms, other immune cells such as mast cells, eosinophils, and macrophages can also release these structures. The different ETs have several features in common, regardless of the type of cells from which they originated, including a DNA backbone with embedded antimicrobial peptides, proteases, and histones. However, they also exhibit remarkable individual differences such as the type of sub-cellular compartments from where the DNA backbone originates (e.g., nucleus or mitochondria), the proportion of responding cells within the pool, and/or the molecular mechanism/s underlying the ETs formation. This review summarizes the knowledge accumulated in recent years regarding the complex and expanding world of ETs and their role in immune function with particular emphasis on the role of other immune cells rather than on neutrophils exclusively. Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10033/269032 2012-01-01T00:00:00Z http://hdl.handle.net/10033/251559 Title: Global transcriptome analysis in influenza-infected mouse lungs reveals the kinetics of innate and adaptive host immune responses. Authors: Pommerenke, Claudia; Wilk, Esther; Srivastava, Barkha; Schulze, Annika; Novoselova, Natalia; Geffers, Robert; Schughart, Klaus Abstract: An infection represents a highly dynamic process involving complex biological responses of the host at many levels. To describe such processes at a global level, we recorded gene expression changes in mouse lungs after a non-lethal infection with influenza A virus over a period of 60 days. Global analysis of the large data set identified distinct phases of the host response. The increase in interferon genes and up-regulation of a defined NK-specific gene set revealed the initiation of the early innate immune response phase. Subsequently, infiltration and activation of T and B cells could be observed by an augmentation of T and B cell specific signature gene expression. The changes in B cell gene expression and preceding chemokine subsets were associated with the formation of bronchus-associated lymphoid tissue. In addition, we compared the gene expression profiles from wild type mice with Rag2 mutant mice. This analysis readily demonstrated that the deficiency in the T and B cell responses in Rag2 mutants could be detected by changes in the global gene expression patterns of the whole lung. In conclusion, our comprehensive gene expression study describes for the first time the entire host response and its kinetics to an acute influenza A infection at the transcriptome level. Sun, 01 Jan 2012 00:00:00 GMT http://hdl.handle.net/10033/251559 2012-01-01T00:00:00Z http://hdl.handle.net/10033/214669 Title: Staphylococcus aureus evades the extracellular antimicrobial activity of mast cells by promoting its own uptake. Authors: Abel, Jens; Goldmann, Oliver; Ziegler, Christina; Höltje, Claudia; Smeltzer, Mark S; Cheung, Ambrose L; Bruhn, Daniela; Rohde, Manfred; Medina, Eva Abstract: In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining the surfaces of the body. We found that bone marrow-derived murine mast cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both the release of extracellular traps as well as discharge of antimicrobial compounds were the mechanisms used by the BMMC to kill extracellular S. aureus. This was accompanied by the secretion of mediators such as TNF-α involved in the recruitment of effector cells. Interestingly, S. aureus subverted the extracellular antimicrobial activity of the BMMC by internalizing within these cells. S. aureus was also capable to internalize within human mast cells (HMC-1) and within murine skin mast cells during in vivo infection. Bacteria internalization was, at least in part, mediated by the α5β1 integrins expressed on the surface of the mast cell. In the intracellular milieu, the bacterium survived and persisted by increasing the cell wall thickness and by gaining access into the mast cell cytosol. The expression of α-hemolysin was essential for staphylococci intracellular persistence. By hiding within the long-life mast cells, staphylococci not only avoid clearance but also establish an infection reservoir that could contribute to chronic carriage. Sat, 01 Jan 2011 00:00:00 GMT http://hdl.handle.net/10033/214669 2011-01-01T00:00:00Z http://hdl.handle.net/10033/203969 Title: Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response. Authors: Nippe, Nadine; Varga, Georg; Holzinger, Dirk; Löffler, Bettina; Medina, Eva; Becker, Karsten; Roth, Johannes; Ehrchen, Jan M; Sunderkötter, Cord Abstract: Staphylococcus aureus is the leading cause of bacterial skin infection. Once it overcomes the epithelial barrier, it either remains locally controlled or spreads in the dermis causing soft tissue infection. These different courses depend not only on its virulence factors, but also on the immune response of the infected individual. The goal of this study was to identify host factors that influence different outcomes. We, therefore, established comparative analysis of subcutaneous footpad infection with S. aureus (SH1000) in different inbred mouse strains. We found that C57BL/6 mice are more susceptible than BALB/c and DBA/2 mice, reflected by significantly higher footpad swelling and bacterial load, as well as increased dissemination of bacteria into inguinal lymph nodes and kidneys. This susceptibility was associated with lower influx of polymorphonuclear leukocytes (PMNs), but higher secretion of CXCL-2. Remarkably, resistance correlated with S. aureus-specific Th2-cell response in BALB/c and DBA/2 mice, whereas susceptible C57BL/6 mice generated a Th1-cell response. As Th1 cells are able to induce release of CXCL-2, and as CXCL-2 is able to increase the survival of S. aureus within PMNs, interactions between PMNs and Th1 or Th2 cells need to be considered as important mechanisms of resistance in murine soft tissue infection with S. aureus. Sat, 01 Jan 2011 00:00:00 GMT http://hdl.handle.net/10033/203969 2011-01-01T00:00:00Z