Myeloid-derived suppressor cells control microbial sepsis.

Abstract

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.

• Authors: Marc Derive, Youcef Bouazza, Corentine Alauzet, Sébastien Gibot
• Journal: Intensive care medicine (Intensive Care Med) Vol. 38 Issue 6 Pg. 1040-9 (Jun 2012) ISSN: 1432-1238 [Electronic] United States
• PMID: 22552586 (Publication Type: Journal Article)

Chemical References

• Antigens, Ly
• CD11b Antigen
• Ly-6C antigen, mouse
• Ly6G antigen, mouse
• Suppressor Factors, Immunologic

Topics

• Animals
• Antigens, Ly (immunology)
• CD11b Antigen (immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Myeloid Cells (metabolism)
• Sepsis (immunology)
• Suppressor Factors, Immunologic (immunology)