HAMLET a human milk protein‐lipid complex induces a pro‐inflammatory phenotype of myeloid cells
| Autor: | Anders Håkansson, Caroline Bergenfelz, Goutham Vansarla |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Immunomodulation and immune therapies Myeloid Cell Survival CD14 Phagocytosis T cell Immunology Oleic Acids Biology p38 Mitogen-Activated Protein Kinases Monocytes Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system medicine Animals Humans Immunology and Allergy Cytotoxic T cell Myeloid Cells dendritic cells Basic Cells Cultured Research Articles alpha‐lactalbumin CD86 Macrophages NF-kappa B Cell biology Phenotype RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure chemistry Lactalbumin Cytokines Research Article|Basic HAMLET (protein complex) Inflammation Mediators HAMLET Signal Transduction 030215 immunology |
| Zdroj: | European Journal of Immunology |
| ISSN: | 1521-4141 0014-2980 |
| DOI: | 10.1002/eji.202048813 |
| Popis: | HAMLET is a protein‐lipid complex with a specific and broad bactericidal and tumoricidal activity, that lacks cytotoxic activity against healthy cells. In this study, we show that HAMLET also has general immune‐stimulatory effects on primary human monocyte‐derived dendritic cells and macrophages (Mo‐DC and Mo‐M) and murine RAW264.7 macrophages. HAMLET, but not its components alpha‐lactalbumin or oleic acid, induces mature CD14low/–CD83+ Mo‐DC and M1‐like CD14+CD86++ Mo‐M surface phenotypes. Concomitantly, inflammatory mediators, including IL‐2, IL‐6, IL‐10, IL‐12 and MIP‐1α, were released in the supernatant of HAMLET‐stimulated cells, indicating a mainly pro‐inflammatory phenotype. The HAMLET‐induced phenotype was mediated by calcium, NFκB and p38 MAPK signaling in Mo‐DCs and calcium, NFκB and ERK signaling in Mo‐M as inhibitors of these pathways almost completely blocked the induction of mature Mo‐DCs and M1‐like Mo‐M. Compared to unstimulated Mo‐DCs, HAMLET‐stimulated Mo‐DCs were more potent in inducing T cell proliferation and HAMLET‐stimulated macrophages were more efficient in phagocytosis of Streptococcus pneumoniae in vitro. This indicates a functionally activated phenotype of HAMLET‐stimulated DCs and macrophages. Combined, we propose that HAMLET has a two‐fold anti‐bacterial activity; one inducing direct cytotoxic activity, the other indirectly mediating elimination of bacteria by activation of immune cells of the myeloid lineage. HAMLET, a human milk protein‐lipid complex induces a pro‐inflammatory phenotype of macrophages and dendritic cells, resulting in augmented release of inflammatory mediators, stimulation of T‐cell proliferation and phagocytosis of pneumococci. We propose that HAMLET's anti‐bacterial activity is two‐fold; one directly bactericidal and the other mediated by activation of myeloid cells. |
| Databáze: | OpenAIRE |
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