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Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model.
Rafiei Hashtchin, Anna; Fehlhaber, Beate; Hetzel, Miriam; Manstein, Felix; Stalp, Jan Lennart; Glage, Silke; Abeln, Markus; Zweigerdt, Robert; Munder, Antje; Viemann, Dorothee; Ackermann, Mania; Lachmann, Nico.
Afiliación
  • Rafiei Hashtchin A; Institute of Experimental Hematology.
  • Fehlhaber B; REBIRTH, Research Center for Translational and Regenerative Medicine.
  • Hetzel M; Department of Pediatric Pneumology, Allergology and Neonatology.
  • Manstein F; Institute of Experimental Hematology.
  • Stalp JL; REBIRTH, Research Center for Translational and Regenerative Medicine.
  • Glage S; REBIRTH, Research Center for Translational and Regenerative Medicine.
  • Abeln M; Department of Cardiothoracic, Transplantation and Vascular Surgery, Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO).
  • Zweigerdt R; Department of Pediatric Pneumology, Allergology and Neonatology.
  • Munder A; Institute for Laboratory Animal Science.
  • Viemann D; Institute for Clinical Biochemistry, Hannover Medical School.
  • Ackermann M; REBIRTH, Research Center for Translational and Regenerative Medicine.
  • Lachmann N; Department of Cardiothoracic, Transplantation and Vascular Surgery, Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO).
Blood Adv ; 5(23): 5190-5201, 2021 12 14.
Article en En | MEDLINE | ID: mdl-34649271
Primary or secondary immunodeficiencies are characterized by disruption of cellular and humoral immunity. Respiratory infections are a major cause of morbidity and mortality among immunodeficient or immunocompromised patients, with Staphylococcus aureus being a common offending organism. We propose here an adoptive macrophage transfer approach aiming to enhance impaired pulmonary immunity against S aureus. Our studies, using human-induced pluripotent stem cell-derived macrophages (iMφs), demonstrate efficient antimicrobial potential against methicillin-sensitive and methicillin-resistant clinical isolates of S aureus. Using an S aureus airway infection model in immunodeficient mice, we demonstrate that the adoptive transfer of iMφs is able to reduce the bacterial load more than 10-fold within 20 hours. This effect was associated with reduced granulocyte infiltration and less damage in lung tissue of transplanted animals. Whole transcriptome analysis of iMφs compared with monocyte-derived macrophages indicates a more profound upregulation of inflammatory genes early after infection and faster normalization 24 hours postinfection. Our data demonstrate high therapeutic efficacy of iMφ-based immunotherapy against S aureus infections and offer an alternative treatment strategy for immunodeficient or immunocompromised patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones del Sistema Respiratorio / Infecciones Estafilocócicas / Células Madre Pluripotentes Inducidas Límite: Animals / Humans Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones del Sistema Respiratorio / Infecciones Estafilocócicas / Células Madre Pluripotentes Inducidas Límite: Animals / Humans Idioma: En Revista: Blood Adv Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos