Bacterial heat shock protein 60, GroEL, can induce the conversion of naïve T cells into a CD4 CD25(+) Foxp3-expressing phenotype

J Innate Immun. 2011;3(6):605-13. doi: 10.1159/000330786. Epub 2011 Sep 5.

Abstract

Recent publications report that heat shock proteins (HSPs) can endow regulatory responses to the systemic immune system when administered via the mucosal route, leading to an amelioration of atherosclerosis and allergy. However, it remains poorly understood if HSP antigens exist in the luminal contents of the gastrointestinal tract and which types of HSP induce regulatory responses. Here we addressed these problems, considering that numerous gut microflora and foods are natural sources of HSPs. SDS-PAGE and immunoblotting with the anti-HSP60 antibody demonstrated the intact and degraded forms of HSP60 mainly in appendix and large intestine of the gastrointestinal tract. No reactivity with this antibody was observed for any of the luminal contents derived from germ-free animals, suggesting gut microflora to be a source of the intestinal HSPs because of lack of HSPs in animal chow diet. GroEL, a typical member of bacterial HSP60, showed a tendency to stimulate splenocytes in germ-free mice, compared to that in conventional mice, suggesting that resident commensal bacterial GroEL may stimulate HSP-reactive T cells as regulatory cells in conventional animals. Importantly, GroEL, but not mouse-derived HSP60, caused naïve T cells to differentiate into CD4(+) CD25(+) Foxp3(+) T cells, indicating that the production of regulatory T cells depends on the type of HSP. Thus, HSPs derived from commensal microbes can be utilized to stimulate immunoregulatory pathways for the maintenance of intestinal homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appendix / metabolism
  • Bacterial Infections / immunology*
  • Bacterial Infections / microbiology
  • Bacterial Proteins / immunology
  • Bacterial Proteins / metabolism*
  • CD4 Antigens / biosynthesis
  • Cell Differentiation
  • Cells, Cultured
  • Chaperonin 60 / immunology
  • Chaperonin 60 / metabolism*
  • Forkhead Transcription Factors / biosynthesis
  • Immunomodulation
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Intestine, Large / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mitochondrial Proteins / immunology
  • Mitochondrial Proteins / metabolism
  • Specific Pathogen-Free Organisms
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Bacterial Proteins
  • CD4 Antigens
  • Chaperonin 60
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Hspd1 protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Mitochondrial Proteins