Myeloid-derived suppressor cells control microbial sepsis.

PURPOSE: To investigate the role of myeloid-derived suppressor cells (MDSCs) during sepsis in mice. MDSCs are a heterogeneous population of cells that expand during cancer, inflammation and infection. These cells, by their ability to suppress T lymphocyte proliferation, regulate immune responses during various diseases. Their role during microbial infections is scarcely known.

METHODS

Septic shock was induced by caecal ligation and puncture in adult male BALB/c mice; sham-operated animals served as controls. Animals were killed under anaesthesia to harvest blood and organs.

RESULTS

Polymicrobial sepsis induced a progressive accumulation of MDSCs in spleens that were found to be enlarged in surviving mice. MDSCs harvested at day 10 after the onset of infection were highly responsive to LPS in terms of cytokines secretion, NF-kB activation, ROS production and arginase I activity, whereas early-appearing (day 3) MDSCs poorly responded to this stimulus. By contrast, both day 3 and day 10 MDSCs were able to inhibit T cell proliferation. Adoptive transfer of day 10 MDSCs to septic mice attenuated peritoneal cytokine production, increased bacterial clearance and dramatically improved survival rate.

CONCLUSION

These results provide new information on the role of MDSCs, suggesting a protective effect during sepsis. Pharmacologic agents known to promote the expansion of MDSCs should thus be further studied for sepsis treatment.