Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model.
Anna Rafiei HashtchinBeate FehlhaberMiriam HetzelFelix MansteinJan Lennart StalpSilke GlageMarkus AbelnRobert ZweigerdtAntje MunderDorothee ViemannMania AckermannNico LachmannPublished in: Blood advances (2022)
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.
Keyphrases
- staphylococcus aureus
- endothelial cells
- biofilm formation
- induced pluripotent stem cells
- methicillin resistant staphylococcus aureus
- high glucose
- pulmonary hypertension
- cell therapy
- immune response
- oxidative stress
- genome wide
- ejection fraction
- cell proliferation
- gene expression
- peripheral blood
- adipose tissue
- dna methylation
- pluripotent stem cells
- dendritic cells
- prognostic factors
- electronic health record
- signaling pathway
- stem cells
- intensive care unit
- autism spectrum disorder
- patient reported outcomes
- diabetic rats
- mesenchymal stem cells
- type diabetes
- cystic fibrosis
- deep learning
- metabolic syndrome
- escherichia coli
- insulin resistance
- bone marrow
- acute respiratory distress syndrome
- artificial intelligence
- data analysis
- climate change
- risk assessment
- respiratory tract