Abstract
BACKGROUND: Mesenchymal stem cells (MSCs) regulate lung inflammation, and enhance bacterial clearance and survival in preclinical models of pneumonia and sepsis1-3,making them a possible treatment for bacterial lung infection resistant to antibiotic therapy.
AIM: We set out to study how MSCs interact with host immunity to reduce bacterial burden and enhance survival through their interaction with regulatory T-cells (Tregs).
METHODS: Bacterial lung infection was studied in a Foxp3-DTR inducible Treg knockout model on a C57Bl/6 genetic background (Kim et al.(2007).Nature Immunol.8(2):191). Foxp3-DTR inducible Treg knockouts carry a targeting construct encoding human diphtheria toxin receptor fused to sequences encoding GFP inserted into the Foxp3 gene. Treatment with diphtheria toxin leads to conditional depletion of Tregs. Age/sex matched groups of transgenics were infected intranasally with either Streptococcal pneumoniae or Pseudomonas aeruginosa. Bone marrow-derived murine MSCs were injected i.v. Mice were monitored for 24 hours before being sacrificed and analysed.
RESULTS: Bacterial clearance was enhanced in MSC-treated mice. Treg depletion impeded the enhanced bacterial clearance seen in MSC treated mice.
CONCLUSIONS: This study shows that MSCs enhance bacterial clearance in the lung and that this effect is Treg dependent.
REFERENCES: 1) Mei S.H.J., et al. (2010). Am J Resp Crit Care Med 182:1047. 2) Krasnodembskaya A., et al. (2012). Am J Physiol Lung Cell Mol Physiol 302:1003. 3) Gupta N., et al. (2012). Thorax. 67(6): 533-539.
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