Journal
BLOOD ADVANCES
Volume 5, Issue 23, Pages 5190-5201Publisher
ELSEVIER
DOI: 10.1182/bloodadvances.2021004853
Keywords
-
Categories
Funding
- Else KroEuroner-Fresenius-Stiftung [2016_A146]
- Federal Ministry of Educa-tion and Research in Germany (BMBF) [01EK1602A]
- REBIRTH Cluster of Excellence [EXC62]
- REBIRTH Research Center for Translational Regenerative Medicine [ZN3440]
- European Society of Clinical Microbiology and Infectious Diseases
- DFG [39087428]
- European Research Council (ERC) [852178]
- German Research Foundation (DFG) [ZW64/4-1, KFO311/ZW64/7-1]
- German Ministry for Education and Sci-ence (BMBF) [13N14086, 01EK1601A, 13XP5092B, 031L0249]
- European Union [66724]
- Deutsches Zentrum fuEuror Lungenfoschung DZL [82DZL002B1]
- European Research Council (ERC) [852178] Funding Source: European Research Council (ERC)
Ask authors/readers for more resources
Primary or secondary immunodeficiencies disrupt cellular and humoral immunity, leading to increased susceptibility to respiratory infections. Adoptive transfer of macrophages can enhance pulmonary immunity against Staphylococcus aureus, reducing bacterial load and tissue damage. Studies demonstrate that induced pluripotent stem cell-derived macrophages are more effective in combating S aureus infections compared to monocyte-derived macrophages.
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 (iM phi s), 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 iM phi s 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 iM phi S 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 iM phi-based immunotherapy against S aureus infections and offer an alternative treatment strategy for immunodeficient or immunocompromised patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available