Hepatic acute phase proteins control innate immune responses during infection by promoting myeloid derived suppressor cell function

  • Leif E. Sander (Creator)
  • Sara Dutton Sackett (Creator)
  • Uta Dierssen (Creator)
  • Naiara Beraza (Creator)
  • Reinhold P. Linke (Creator)
  • Michael Muller (Creator)
  • Julie Magarian Blander (Creator)
  • Frank Tacke (Creator)
  • Christian Trautwein (Creator)



Acute phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and anti-inflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a murine model for polymicrobial sepsis we show here that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6-family cytokines, dramatically increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through signal transducer and activator of transcription (Stat)3 was required to control systemic inflammation. Notably, hepatic gp130/Stat3 activation was also a prerequisite to facilitate mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for anti-inflammatory properties in cancer. We show that MDSCs were critical to regulate innate inflammation and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. We identified serum amyloid A and Cxcl-1/KC as hepatic acute phase genes that cooperatively promoted MDSC mobilization, accumulation and survival. Administration of these proteins efficiently elevated MDSC numbers and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through acute phase proteins critically controls inflammatory responses during infection.
Date made available27 May 2010
PublisherWageningen University


  • Mus musculus

Accession numbers

  • GSE22009
  • PRJNA127473

Cite this