Abstract
Bone marrow-derived mesenchymal stromal cells (MSC) possess an immune plasticity manifested by either an immunosuppressive or, when activated with IFN-γ, an APC phenotype. Herein, TLR expression by MSC and their immune regulatory role were investigated. We observed that human MSC and macrophages expressed TLR3 and TLR4 at comparable levels and TLR-mediated activation of MSC resulted in the production of inflammatory mediators such as IL-1β, IL-6, IL-8/CXCL8, and CCL5. IFN-α or IFN-γ priming up-regulated production of these inflammatory mediators and expression of IFNB, inducible NO synthase (iNOS), and TRAIL upon TLR activation in MSC and macrophages, but failed to induce IL-12 and TNF-α production in MSC. Nonetheless, TLR activation in MSC resulted in the formation of an inflammatory site attracting innate immune cells, as evaluated by human neutrophil chemotaxis assays and by the analysis of immune effectors retrieved from Matrigel-embedded MSC injected into mice after in vitro preactivation with cytokines and/or TLR ligands. Hence, TLR-activated MSC are capable of recruiting immune inflammatory cells. In addition, IFN priming combined with TLR activation may increase immune responses induced by Ag-presenting MSC through presentation of Ag in an inflammatory context, a mechanism that could be applied in a cell-based vaccine.
Footnotes
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↵1 This work was supported by a Terry Fox Foundation New Frontiers Program Project Grant and by the Canadian Institute for Health Research Operating Grant MOP-15017. M.F. is a PhD candidate at McGill University and is the recipient of a Canadian Institute for Health Research Studentship and J.G. is a Fonds de Recherché en Santé du Québec Chercheur Senior.
↵2 R.R.-M. and M.F. contributed equally to this study.
↵3 Address correspondence and reprint requests to Dr. Jacques Galipeau, Department of Medicine and Oncology, Sir Mortimer B. Davis Jewish General Hospital & Lady Davis Institute for Medical Research, McGill University, 3755 Cote Sainte-Catherine Road, Montreal, Quebec, Canada H3T 1E2. E-mail address: jacques.galipeau{at}mcgill.ca
- Received November 18, 2008.
- Accepted April 16, 2009.
- Copyright © 2009 by The American Association of Immunologists, Inc.