{"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T06:48:36Z","author":[{"last_name":"Martins","first_name":"Rui","full_name":"Martins, Rui"},{"last_name":"Maier","first_name":"Julia","full_name":"Maier, Julia"},{"full_name":"Gorki, Anna","first_name":"Anna","last_name":"Gorki"},{"full_name":"Huber, Kilian","first_name":"Kilian","last_name":"Huber"},{"last_name":"Sharif","first_name":"Omar","full_name":"Sharif, Omar"},{"full_name":"Starkl, Philipp","first_name":"Philipp","last_name":"Starkl"},{"full_name":"Saluzzo, Simona","last_name":"Saluzzo","first_name":"Simona"},{"full_name":"Quattrone, Federica","first_name":"Federica","last_name":"Quattrone"},{"last_name":"Gawish","first_name":"Riem","full_name":"Gawish, Riem"},{"full_name":"Lakovits, Karin","first_name":"Karin","last_name":"Lakovits"},{"full_name":"Aichinger, Michael","first_name":"Michael","last_name":"Aichinger"},{"first_name":"Branka","last_name":"Radic Sarikas","full_name":"Radic Sarikas, Branka"},{"full_name":"Lardeau, Charles","first_name":"Charles","last_name":"Lardeau"},{"last_name":"Hladik","first_name":"Anastasiya","full_name":"Hladik, Anastasiya"},{"last_name":"Korosec","first_name":"Ana","full_name":"Korosec, Ana"},{"last_name":"Brown","id":"3DAB9AFC-F248-11E8-B48F-1D18A9856A87","first_name":"Markus","full_name":"Brown, Markus"},{"full_name":"Vaahtomeri, Kari","first_name":"Kari","id":"368EE576-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7829-3518","last_name":"Vaahtomeri"},{"first_name":"Michelle","id":"2EDEA62C-F248-11E8-B48F-1D18A9856A87","last_name":"Duggan","full_name":"Duggan, Michelle"},{"full_name":"Kerjaschki, Dontscho","first_name":"Dontscho","last_name":"Kerjaschki"},{"first_name":"Harald","last_name":"Esterbauer","full_name":"Esterbauer, Harald"},{"first_name":"Jacques","last_name":"Colinge","full_name":"Colinge, Jacques"},{"first_name":"Stephanie","last_name":"Eisenbarth","full_name":"Eisenbarth, Stephanie"},{"first_name":"Thomas","last_name":"Decker","full_name":"Decker, Thomas"},{"full_name":"Bennett, Keiryn","first_name":"Keiryn","last_name":"Bennett"},{"full_name":"Kubicek, Stefan","first_name":"Stefan","last_name":"Kubicek"},{"full_name":"Sixt, Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-6620-9179","first_name":"Michael K"},{"first_name":"Giulio","last_name":"Superti Furga","full_name":"Superti Furga, Giulio"},{"first_name":"Sylvia","last_name":"Knapp","full_name":"Knapp, Sylvia"}],"doi":"10.1038/ni.3590","quality_controlled":"1","_id":"1142","year":"2016","citation":{"short":"R. Martins, J. Maier, A. Gorki, K. Huber, O. Sharif, P. Starkl, S. Saluzzo, F. Quattrone, R. Gawish, K. Lakovits, M. Aichinger, B. Radic Sarikas, C. Lardeau, A. Hladik, A. Korosec, M. Brown, K. Vaahtomeri, M. Duggan, D. Kerjaschki, H. Esterbauer, J. Colinge, S. Eisenbarth, T. Decker, K. Bennett, S. Kubicek, M.K. Sixt, G. Superti Furga, S. Knapp, Nature Immunology 17 (2016) 1361–1372.","ieee":"R. Martins <i>et al.</i>, “Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions,” <i>Nature Immunology</i>, vol. 17, no. 12. Nature Publishing Group, pp. 1361–1372, 2016.","apa":"Martins, R., Maier, J., Gorki, A., Huber, K., Sharif, O., Starkl, P., … Knapp, S. (2016). Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. <i>Nature Immunology</i>. Nature Publishing Group. <a href=\"https://doi.org/10.1038/ni.3590\">https://doi.org/10.1038/ni.3590</a>","ama":"Martins R, Maier J, Gorki A, et al. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. <i>Nature Immunology</i>. 2016;17(12):1361-1372. doi:<a href=\"https://doi.org/10.1038/ni.3590\">10.1038/ni.3590</a>","chicago":"Martins, Rui, Julia Maier, Anna Gorki, Kilian Huber, Omar Sharif, Philipp Starkl, Simona Saluzzo, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” <i>Nature Immunology</i>. Nature Publishing Group, 2016. <a href=\"https://doi.org/10.1038/ni.3590\">https://doi.org/10.1038/ni.3590</a>.","mla":"Martins, Rui, et al. “Heme Drives Hemolysis-Induced Susceptibility to Infection via Disruption of Phagocyte Functions.” <i>Nature Immunology</i>, vol. 17, no. 12, Nature Publishing Group, 2016, pp. 1361–72, doi:<a href=\"https://doi.org/10.1038/ni.3590\">10.1038/ni.3590</a>.","ista":"Martins R, Maier J, Gorki A, Huber K, Sharif O, Starkl P, Saluzzo S, Quattrone F, Gawish R, Lakovits K, Aichinger M, Radic Sarikas B, Lardeau C, Hladik A, Korosec A, Brown M, Vaahtomeri K, Duggan M, Kerjaschki D, Esterbauer H, Colinge J, Eisenbarth S, Decker T, Bennett K, Kubicek S, Sixt MK, Superti Furga G, Knapp S. 2016. Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions. Nature Immunology. 17(12), 1361–1372."},"publication":"Nature Immunology","month":"12","main_file_link":[{"url":"https://ora.ox.ac.uk/objects/uuid:f53a464e-1e5b-4f08-a7d8-b6749b852b9d","open_access":"1"}],"scopus_import":1,"volume":17,"publication_status":"published","acknowledgement":"Y. Fukui (Medical Institute of Bioregulation, Kyushu University) and J. Stein (Theodor Kocher Institute, University of Bern) are acknowledged for providing the DOCK8 deficient bone marrow. and H. Häcker (St. Judes Children's Research Hospital) for providing the ERHBD-HoxB8-encoding retroviral construct. pSpCas9(BB)-2a-Puro (PX459) was a gift from F. Zhang (Massachusetts Institute of Technology) (Addgene plasmid # 48139) and pGRG36 was a gift from N. Craig (Johns Hopkins University School of Medicine) (Addgene plasmid # 16666). LifeAct-GFP-encoding retrovirus was kindly provided by A. Leithner (Institute of Science and Technology Austria). pSIM8 and TKC E. coli were gifts from D.L. Court (Center for Cancer Research, National Cancer Institute). We acknowledge M. Gröger and S. Rauscher for excellent technical support (Core imaging facility, Medical University of Vienna). We thank D.P. Barlow and L.R. Cheever for critical reading of the manuscript. This work was supported by the Austrian Academy of Sciences, the Science Fund of the Austrian National Bank (14107) and the Austrian Science Fund FWF (I1620-B22) in the Infect-ERA framework (to S.Knapp).","status":"public","title":"Heme drives hemolysis-induced susceptibility to infection via disruption of phagocyte functions","language":[{"iso":"eng"}],"date_created":"2018-12-11T11:50:22Z","intvolume":"        17","day":"01","issue":"12","page":"1361 - 1372","publisher":"Nature Publishing Group","publist_id":"6216","type":"journal_article","date_published":"2016-12-01T00:00:00Z","oa_version":"Submitted Version","abstract":[{"text":"Hemolysis drives susceptibility to bacterial infections and predicts poor outcome from sepsis. These detrimental effects are commonly considered to be a consequence of heme-iron serving as a nutrient for bacteria. We employed a Gram-negative sepsis model and found that elevated heme levels impaired the control of bacterial proliferation independently of heme-iron acquisition by pathogens. Heme strongly inhibited phagocytosis and the migration of human and mouse phagocytes by disrupting actin cytoskeletal dynamics via activation of the GTP-binding Rho family protein Cdc42 by the guanine nucleotide exchange factor DOCK8. A chemical screening approach revealed that quinine effectively prevented heme effects on the cytoskeleton, restored phagocytosis and improved survival in sepsis. These mechanistic insights provide potential therapeutic targets for patients with sepsis or hemolytic disorders.","lang":"eng"}],"oa":1,"department":[{"_id":"MiSi"},{"_id":"PeJo"}]}