Cargando…

Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Hematology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153022/
https://www.ncbi.nlm.nih.gov/pubmed/34649271
http://dx.doi.org/10.1182/bloodadvances.2021004853
_version_ 1784717764403920896
author 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
author_facet 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
author_sort Rafiei Hashtchin, Anna
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9153022
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Society of Hematology
record_format MEDLINE/PubMed
spelling pubmed-91530222022-05-31 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 Blood Adv Immunobiology and Immunotherapy 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. American Society of Hematology 2021-12-07 /pmc/articles/PMC9153022/ /pubmed/34649271 http://dx.doi.org/10.1182/bloodadvances.2021004853 Text en © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
spellingShingle Immunobiology and Immunotherapy
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
Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
title Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
title_full Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
title_fullStr Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
title_full_unstemmed Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
title_short Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
title_sort human ipsc-derived macrophages for efficient staphylococcus aureus clearance in a murine pulmonary infection model
topic Immunobiology and Immunotherapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153022/
https://www.ncbi.nlm.nih.gov/pubmed/34649271
http://dx.doi.org/10.1182/bloodadvances.2021004853
work_keys_str_mv AT rafieihashtchinanna humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT fehlhaberbeate humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT hetzelmiriam humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT mansteinfelix humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT stalpjanlennart humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT glagesilke humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT abelnmarkus humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT zweigerdtrobert humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT munderantje humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT viemanndorothee humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT ackermannmania humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel
AT lachmannnico humanipscderivedmacrophagesforefficientstaphylococcusaureusclearanceinamurinepulmonaryinfectionmodel