Skip to main content
eScholarship
Open Access Publications from the University of California

Type I interferon signaling in hematopoietic cells is required for survival in mouse polymicrobial sepsis by regulating CXCL10.

  • Author(s): Kelly-Scumpia, Kindra M
  • Scumpia, Philip O
  • Delano, Matthew J
  • Weinstein, Jason S
  • Cuenca, Alex G
  • Wynn, James L
  • Moldawer, Lyle L
  • et al.
Abstract

Type I interferon (IFN) alpha/beta is critical for host defense. During endotoxicosis or highly lethal bacterial infections where systemic inflammation predominates, mice deficient in IFN-alpha/beta receptor (IFNAR) display decreased systemic inflammation and improved outcome. However, human sepsis mortality often occurs during a prolonged period of immunosuppression and not from exaggerated inflammation. We used a low lethality cecal ligation and puncture (CLP) model of sepsis to determine the role of type I IFNs in host defense during sepsis. Despite increased endotoxin resistance, IFNAR(-/-) and chimeric mice lacking IFNAR in hematopoietic cells display increased mortality to CLP. This was not associated with an altered early systemic inflammatory response, except for decreased CXCL10 production. IFNAR(-/-) mice display persistently elevated peritoneal bacterial counts compared with wild-type mice, reduced peritoneal neutrophil recruitment, and recruitment of neutrophils with poor phagocytic function despite normal to enhanced adaptive immune function during sepsis. Importantly, CXCL10 treatment of IFNAR(-/-) mice improves survival and decreases peritoneal bacterial loads, and CXCL10 increases mouse and human neutrophil phagocytosis. Using a low lethality sepsis model, we identify a critical role of type I IFN-dependent CXCL10 in host defense during polymicrobial sepsis by increasing neutrophil recruitment and function.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
Current View