IFN-gamma regulated chemokine production determines the outcome of Staphylococcus aureus infection

J Immunol. 2008 Jul 15;181(2):1323-32. doi: 10.4049/jimmunol.181.2.1323.


Immunomodulatory therapy represents an attractive approach in treating multidrug-resistant infections. Developing this therapy necessitates a lucid understanding of host defense mechanisms. Neutrophils represent the first line of systemic defense during Staphylococcus aureus infections. However, recent research suggests that survival of S. aureus inside neutrophils may actually contribute to pathogenesis, indicating that neutrophil trafficking to the infection site must be tightly regulated to ensure efficient microbial clearance. We demonstrate that neutrophil-regulating T cells are activated during S. aureus infection and produce cytokines that control the local neutrophil response. S. aureus capsular polysaccharide activates T cell production of IFN-gamma in a novel MHC class II-dependent mechanism. During S. aureus surgical wound infection, the presence of IFN-gamma at the infection site depends upon alphabetaTCR+ cells and functions to regulate CXC chemokine production and neutrophil recruitment in vivo. We note that the reduced neutrophil response seen in IFN-gamma-/- mice during S. aureus infection is associated with reduced tissue bacterial burden. CXC chemokine administration to the infection site resulted in an increased survival of viable S. aureus inside neutrophils isolated from the wound. These data demonstrate that T cell-derived IFN-gamma generates a neutrophil-rich environment that can potentiate S. aureus pathogenesis by facilitating bacterial survival within the neutrophil. These findings suggest avenues for novel immunomodulatory approaches to control S. aureus infections.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Chemokines, CXC / immunology
  • Chemokines, CXC / metabolism*
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism*
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / microbiology
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophil Infiltration
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • Neutrophils / metabolism
  • Neutrophils / microbiology
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / immunology
  • Surgical Wound Infection / immunology*
  • Surgical Wound Infection / microbiology


  • Antigens, Bacterial
  • Chemokines, CXC
  • Histocompatibility Antigens Class II
  • Interferon-gamma