Adaptive immunity to murine skin commensals

Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):E2977-86. doi: 10.1073/pnas.1401820111. Epub 2014 Jul 7.

Abstract

The adaptive immune system provides critical defense against pathogenic bacteria. Commensal bacteria have begun to receive much attention in recent years, especially in the gut where there is growing evidence of complex interactions with the adaptive immune system. In the present study, we observed that commensal skin bacteria are recognized by major populations of T cells in skin-draining lymph nodes of mice. Recombination activating gene 1 (Rag1)(-/-) mice, which lack adaptive immune cells, contained living skin-derived bacteria and bacterial sequences, especially mycobacteria, in their skin-draining lymph nodes. T cells from skin-draining lymph nodes of normal mice were shown, in vitro, to specifically recognize bacteria of several species that were grown from Rag1(-/-) lymph nodes. T cells from skin-draining lymph nodes, transferred into Rag1(-/-) mice proliferated in skin-draining lymph nodes, expressed a restricted T-cell receptor spectrotype and produced cytokines. Transfer of T cells into Rag1(-/-) mice had the effect of reducing bacterial sequences in skin-draining lymph nodes and in skin itself. Antibacterial effects of transferred T cells were dependent on IFNγ and IL-17A. These studies suggest a previously unrecognized role for T cells in controlling skin commensal bacteria and provide a mechanism to account for cutaneous infections and mycobacterial infections in T-cell-deficient patients.

Keywords: T lymphocyte; microbiome.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • Antigens / immunology
  • Bacteria / immunology*
  • Cell Proliferation
  • Cytokines / metabolism
  • Homeodomain Proteins / metabolism
  • Immunologic Memory
  • Interferon-gamma / metabolism
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Phenotype
  • RNA, Ribosomal, 16S / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism
  • Skin / immunology*
  • Skin / microbiology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology

Substances

  • Antigens
  • Cytokines
  • Homeodomain Proteins
  • RNA, Ribosomal, 16S
  • Receptors, Antigen, T-Cell, alpha-beta
  • RAG-1 protein
  • Interferon-gamma