PT  - JOURNAL ARTICLE
AU  - Rosemary J. Boyton
AU  - Janet Stowell
AU  - Catherine Reynolds
AU  - Kathryn Quigley
AU  - Daniel Altmann
AU  - Francesco Dazzi
TI  - Mesenchymal stem cells enhance bacterial clearance of streptococcal <em>pneumonia</em>e and pseudomonas <em>aeruginosa</em> in the lung
AID  - 10.1183/13993003.congress-2016.PA2624
DP  - 2016 Sep 01
TA  - European Respiratory Journal
PG  - PA2624
VI  - 48
IP  - suppl 60
4099  - http://erj.ersjournals.com/content/48/suppl_60/PA2624.short
4100  - http://erj.ersjournals.com/content/48/suppl_60/PA2624.full
SO  - Eur Respir J2016 Sep 01; 48
AB  - 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.