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Toll-like receptor-3-activated human mesenchymal stromal cells significantly prolong the survival and function of neutrophils
- Source :
- STEM CELLS; Vol 29
- Publication Year :
- 2011
-
Abstract
- Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are stromal precursors endowed with extensive immunomodulative properties. In this study, we aimed to assess whether Toll-like receptor-3 (TLR3)- and TLR4-activated BM-MSC influence human neutrophil (PMN) responses under coculture conditions. We show that TLR3 triggering by polyinosinic:polycytidylic acid dramatically amplifies, in a more significant manner than TLR4 triggering by lipopolysaccharide, the antiapoptotic effects that resting BM-MSC constitutively exert on PMN under coculture conditions, preserving a significant fraction of viable and functional PMN up to 72 hours. In addition, TLR3- and TLR4-activated BM-MSC enhance respiratory burst ability and CD11b expression by PMN. The coculture in the absence of cell contact and the incubation of PMN in supernatants harvested from TLR3- and TLR4-activated BM-MSC yield comparable results in terms of increased survival and immunophenotypic changes, thus suggesting the involvement of endogenous soluble factors. Neutralizing experiments reveal that the biological effects exerted on PMN by TLR3-activated BM-MSC are mediated by the combined action of interleukin 6, interferon-β (IFN-β), and granulocyte macrophage colony-stimulating factor (GM-CSF), while those exerted by TLR4-activated BM-MSC mostly depend on GM-CSF. MSC isolated from thymus, spleen, and subcutaneous adipose tissue behaves similarly. Finally, the effects exerted by TLR3- or TLR4-stimulated BM-MSC on PMN are conserved even after the previous priming of BM-MSC with IFN-γ and tumor necrosis factor-α. Our data highlight a novel mechanism by which MSC sustain and amplify the functions of PMN in response to TLR3- and TLR4-triggering and may consequently contribute to inflammatory disorders.
- Subjects :
- Lipopolysaccharides
Stromal cell
Cell Survival
Neutrophils
Bone Marrow Cells
Toll-like receptor(TLR)3
Biology
Granulocyte
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Granulocyte Colony-Stimulating Factor
medicine
Humans
Cells, Cultured
030304 developmental biology
0303 health sciences
Toll-like receptor
Interleukin-6
Tumor Necrosis Factor-alpha
TLR4-activated BM-MSC
Bone marrow-derived mesenchymal stromal cells (BM-MSC)
neutrophil responses
Mesenchymal stem cell
hemic and immune systems
Mesenchymal Stem Cells
Cell Biology
Interferon-beta
Coculture Techniques
Cell biology
Respiratory burst
Toll-Like Receptor 3
medicine.anatomical_structure
Phenotype
Poly I-C
030220 oncology & carcinogenesis
Culture Media, Conditioned
Immunology
TLR4
Molecular Medicine
Tumor necrosis factor alpha
Stem cell
Developmental Biology
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- STEM CELLS; Vol 29
- Accession number :
- edsair.doi.dedup.....cc766ebe794a71ad32031f2cefaf2319