Proteomic and bioinformatic profiling of neutrophils in CLL reveals functional defects that predispose to bacterial infections.

Autor:	Subramaniam N; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Bayer AG, Pharma Research Center, Wuppertal, Germany., Bottek J; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Thiebes S; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Zec K; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Kudla M; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Soun C; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany., de Dios Panal E; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; University Medical Centre Utrecht, Center for Translational Immunology, Utrecht, The Netherlands., Lill JK; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Leibniz-Institut für Analytische Wissenschaften, Leibniz-Institut für Analytische Wissenschaften (ISAS-e.V.), Dortmund, Germany., Pfennig A; Genome Informatics, Institute of Human Genetics., Herrmann R; Division of Neonatology, Kinderklinik I, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Bruderek K; Research Division, Department of Otorhinolaryngology, University Hospital Essen, West German Cancer Center, Essen, Germany., Rahmann S; Genome Informatics, Institute of Human Genetics., Brandau S; Research Division, Department of Otorhinolaryngology, University Hospital Essen, West German Cancer Center, Essen, Germany., Johansson P; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, German Consortium for Translational Cancer Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Reinhardt HC; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, German Consortium for Translational Cancer Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Dürig J; Department of Hematology and Stem Cell Transplantation, West German Cancer Center, German Consortium for Translational Cancer Research, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Seiffert M; Molecular Genetics, German Cancer Research Center, Heidelberg, Germany., Bracht T; Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, Bochum, Germany; and.; Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Germany., Sitek B; Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, Bochum, Germany; and., Engel DR; Institute of Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2021 Mar 09; Vol. 5 (5), pp. 1259-1272.
DOI:	10.1182/bloodadvances.2020002949
Abstrakt:	Patients with chronic lymphocytic leukemia (CLL) typically suffer from frequent and severe bacterial infections. Although it is well known that neutrophils are critical innate immune cells facilitating the early defense, the underlying phenotypical and functional changes in neutrophils during CLL remain largely elusive. Using a murine adoptive transfer model of CLL, we demonstrate aggravated bacterial burden in CLL-bearing mice upon a urinary tract infection with uropathogenic Escherichia coli. Bioinformatic analyses of the neutrophil proteome revealed increased expression of proteins associated with interferon signaling and decreased protein expression associated with granule composition and neutrophil migration. Functional experiments validated these findings by showing reduced levels of myeloperoxidase and acidification of neutrophil granules after ex vivo phagocytosis of bacteria. Pathway enrichment analysis indicated decreased expression of molecules critical for neutrophil recruitment, and migration of neutrophils into the infected urinary bladder was significantly reduced. These altered migratory properties of neutrophils were also associated with reduced expression of CD62L and CXCR4 and correlated with an increased incidence of infections in patients with CLL. In conclusion, this study describes a molecular signature of neutrophils through proteomic, bioinformatic, and functional analyses that are linked to a reduced migratory ability, potentially leading to increased bacterial infections in patients with CLL. (© 2021 by The American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu