Dendritic cells are central coordinators of the host immune response to Staphylococcus aureus bloodstream infection

Am J Pathol. 2012 Oct;181(4):1327-37. doi: 10.1016/j.ajpath.2012.06.039. Epub 2012 Aug 10.


Dendritic cells (DCs) play an important role in integration of the immune responses induced by pathogens. The purpose of this study was to determine the importance of DCs in host defense against Staphylococcus aureus bacteremia. Using a murine infection model, we demonstrated that DCs are rapidly recruited into infected tissue after intravenous inoculation with S. aureus. The recruited DCs were fully functional and in a more advanced stage of maturation than those isolated from uninfected mice. Depletion of DCs in CD11c-DTR transgenic mice resulted in substantial worsening of infection, as indicated by increased bacterial loads in kidneys and lungs, accelerated mortality, and more severe pathology. Furthermore, DC depletion completely abolished IL-12 production in response to infection. The beneficial effect afforded by DCs during S. aureus infection was not mediated by their contribution to direct bacterial killing, nor by increased neutrophil recruitment. Instead, neutrophil influx (along with expression of CXC chemokines) was significantly enhanced in infected tissue after depletion of DCs. We also found that the bactericidal capacity of the recruited neutrophils was significantly impaired in DC-depleted mice. More importantly, the detrimental effect of DC depletion was practically reversed by treatment with exogenous recombinant mouse IL-12. Our results demonstrated that DCs, probably through their production of IL-12, play an important role in coordinating the inflammatory response during S. aureus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / blood
  • Bacteremia / complications
  • Bacteremia / microbiology
  • Bacteremia / pathology
  • CD11c Antigen / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Dendritic Cells / pathology
  • Dendritic Cells / ultrastructure
  • Host-Pathogen Interactions / drug effects
  • Host-Pathogen Interactions / immunology*
  • Immunity / drug effects
  • Immunity / immunology*
  • Inflammation / blood
  • Inflammation / complications
  • Inflammation / pathology
  • Interleukin-12 / administration & dosage
  • Interleukin-12 / metabolism
  • Interleukin-12 / pharmacology
  • Lung / drug effects
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Microbial Viability / drug effects
  • Neutrophil Infiltration / drug effects
  • Phagocytosis / drug effects
  • Spleen / drug effects
  • Spleen / immunology
  • Spleen / microbiology
  • Spleen / pathology
  • Staphylococcal Infections / blood*
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / ultrastructure


  • CD11c Antigen
  • Interleukin-12