Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model
Hashtchin AR, Fehlhaber B, Hetzel M, Manstein F, Stalp JL, Glage S, Abeln M, Zweigerdt R, Munder A, Viemann D, Ackermann M, Lachmann N (2021)
Publication Type: Journal article
Publication year: 2021
Journal
Book Volume: 5
Pages Range: 5190-5201
DOI: 10.1182/bloodadvances.2021004853
Abstract
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 cellderived macrophages (iMws), 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 iMws 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 iMws 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 iMw-based immunotherapy against S aureus infections and offer an alternative treatment strategy for immunodeficient or immunocompromised patients.
Involved external institutions
Germany (DE)How to cite
APA:
Hashtchin, A.R., Fehlhaber, B., Hetzel, M., Manstein, F., Stalp, J.L., Glage, S.,... Lachmann, N. (2021). Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model. Blood Advances, 5, 5190-5201. https://doi.org/10.1182/bloodadvances.2021004853
MLA:
Hashtchin, Anna Rafiei, et al. "Human iPSC-derived macrophages for efficient Staphylococcus aureus clearance in a murine pulmonary infection model." Blood Advances 5 (2021): 5190-5201.
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