A Paradoxical Role for Myeloid-Derived Suppressor Cells in Sepsis and Trauma

Table 2 Functional properties of MDSCs.^a

	Pathologic process	Mechanism/function	Reference(s)
Upregulated MDSC function
Arginase (ARG)	Cancer	l-arginine depletion and NO scavenging	(2,24)
Inducible nitric oxide synthetase	Cancer	l-arginine depletion and bactericidal	(2,24)
NADPH oxidase	Cancer	ROS/RNS production, nitrosylation of TCR, and bactericidal	(20,25)
M-CSF R (CD115)	Cancer	Associated with suppressive activity	(23,60)
IL-4rα (CD124)	Cancer	Th2 skewing and associated with suppressive activity	(9,14,23)
Proinflammatory cytokines
IL-1β	Cancer	Inflammation	(61)
TNF-α	Cancer, Sepsis	Inflammation	(12,27,61)
LTA4H	Cancer	Inflammation	(27)
MIP-1β	Sepsis	Inflammation; chemokine	(12)
CXCL10	Cancer	Inflammation; chemokine	(61)
RANTES	Sepsis	Inflammation; chemokine	(12)
T-helper cell 2 skewing/antiinflammatory cytokines
IL-10	Sepsis	Antiinflammatory; inhibits T-cell responses; causes TRC expansion	(12)
IL-13	Cancer	Th2-polarizing cytokine	(9)
Immunosuppression
Direct antigen-specific CD8⁺ T-cell anergy	Cancer	MHC restricted dissociation of CD3ζ/TCR signaling	(25)
Indirect antigen-specific CD8⁺ T-cell anergy	Cancer	ARG, ROS, iNOS	(2,14,26)
Indirect antigen-specific CD4⁺ T-cell anergy	Cancer	ARG	(2,26)
TRC expansion	Cancer	CD40, IL-10	(62)
Suppression of graft-versus-host disease	Cancer	IL-10 and TCR activation	(63)
Protection against infection
Protection against primary infection	Sepsis	Regulation of innate inflammation	(28)
Protection against secondary infection	Burn	Increases PMNs and inflammatory monocytes	(30)

^aMDSCs are known to be pluripotent, affecting both innate and adaptive immunity through direct contact and the secretion of various soluble factors (including iNOS, ROS and cytokines). These properties are responsible for both the immunosuppressive function of MDSCs as well as their protective role against primary and secondary infection.

ISSN: 1528-3658