Interleukin-6 is essential for zwitterionic polysaccharide-mediated abscess formation

Innate Immun. 2010 Oct;16(5):310-21. doi: 10.1177/1753425909346974. Epub 2009 Nov 6.

Abstract

Abscess formation associated with secondary peritonitis causes severe morbidity and can be fatal. Formation of abscesses requires the presence of CD4+ T-cells. Zwitterionic polysaccharides (ZPSs) represent a novel class of immunomodulatory bacterial antigens that stimulate CD4+ T-cells in a major histocompatibility complex (MHC) class II-dependent manner. The capsular polysaccharide Sp1 of Streptococcus pneumoniae serotype 1 possesses a zwitterionic charge with free amino groups and promotes T-cell-dependent abscess formation in an experimental mouse model. So far, nothing is known about the function of Interleukin (IL)-6 in intraperitoneal abscess formation. Here, we demonstrate that macrophages and dendritic cells (DCs), the most prevalent professional antigen-presenting cells involved in the formation of abscesses, secrete Interleukin (IL)-6 and are incorporated in the abscess capsule. Sp1 inhibits apoptosis of CD4+ T-cells and causes IL-17 expression by CD4+ T-cells in an IL-6-dependent manner. Abrogation of the Sp1-induced pleiotropic effects of IL-6 in IL-6-deficient mice and mice treated with an IL-6-specific neutralizing antibody results in significant inhibition of abscess formation. The data delineate the essential role of IL-6 in the linkage of innate and adaptive immunity in polysaccharide-mediated abscess formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscess / immunology*
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Antigen-Presenting Cells / pathology
  • Bacterial Capsules / immunology
  • Bacterial Capsules / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Movement
  • Cell Survival
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Dendritic Cells / pathology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Peritoneal Cavity / pathology
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / immunology
  • Polysaccharides, Bacterial / metabolism
  • Protein Binding
  • Streptococcus pneumoniae / immunology*

Substances

  • Histocompatibility Antigens Class II
  • Polysaccharides, Bacterial