@article{HungDreherDiessneretal.2022,
  author    = {Hung, Sophia and Dreher, Liane and Diessner, Joachim and Schwarz, Stefan and Ohlsen, Knut and Hertlein, Tobias},
  title     = {MRSA infection in the thigh muscle leads to systemic disease, strong inflammation, and loss of human monocytes in humanized mice},
  series = {Frontiers in Immunology},
  volume    = {13},
  journal   = {Frontiers in Immunology},
  issn      = {1664-3224},
  doi       = {10.3389/fimmu.2022.892053},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-278050},
  year      = {2022},
  abstract  = {MRSA (Methicillin-resistant Staphylococcus aureus) is the second-leading cause of deaths by antibiotic-resistant bacteria globally, with more than 100,000 attributable deaths annually. Despite the high urgency to develop a vaccine to control this pathogen, all clinical trials with pre-clinically effective candidates failed so far. The recent development of "humanized" mice might help to edge the pre-clinical evaluation closer to the clinical situation and thus close this gap. We infected humanized NSG mice (huNSG: (NOD)-scid IL2R\(_γ\)\(^{null}\) mice engrafted with human CD34+ hematopoietic stem cells) locally with S. aureus USA300 LAC* lux into the thigh muscle in order to investigate the human immune response to acute and chronic infection. These mice proved not only to be more susceptible to MRSA infection than wild-type or "murinized" mice, but displayed furthermore inferior survival and signs of systemic infection in an otherwise localized infection model. The rate of humanization correlated directly with the severity of disease and survival of the mice. Human and murine cytokine levels in blood and at the primary site of infection were strongly elevated in huNSG mice compared to all control groups. And importantly, differences in human and murine immune cell lineages surfaced during the infection, with human monocyte and B cell numbers in blood and bone marrow being significantly reduced at the later time point of infection. Murine monocytes in contrast behaved conversely by increasing cell numbers. This study demonstrates significant differences in the in vivo behavior of human and murine cells towards S. aureus infection, which might help to sharpen the translational potential of pre-clinical models for future therapeutic approaches.},
  language  = {en}
}
@article{SoehnleinDrechslerDoeringetal.2013,
  author    = {Soehnlein, Oliver and Drechsler, Maik and D{\"o}ring, Yvonne and Lievens, Dirk and Hartwig, Helene and Kemmerich, Klaus and Ortega-G{\´o}mez, Almudena and Mandl, Manuela and Vijayan, Santosh and Projahn, Delia and Garlichs, Christoph D. and Koenen, Rory R. and Hristov, Mihail and Lutgens, Esther and Zernecke, Alma and Weber, Christian},
  title     = {Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes},
  series = {EMBO Molecular Medicine},
  volume    = {5},
  journal   = {EMBO Molecular Medicine},
  issn      = {1757-4676},
  doi       = {10.1002/emmm.201201717},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122204},
  pages     = {471-481},
  year      = {2013},
  abstract  = {We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical \((inflammatory/Gr1^{hi})\) or non-classical \((resident/Gr1^{lo})\) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient \((Apoe^{-/-})\) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient \(Apoe^{-/-}\) mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or \(CX_3CR1\) in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment.},
  language  = {en}
}