Immunostimulatory Effects Triggered by Enterococcus faecalis CECT7121 Probiotic Strain Involve Activation of Dendritic Cells and Interferon-Gamma Production

PLoS One. 2015 May 15;10(5):e0127262. doi: 10.1371/journal.pone.0127262. eCollection 2015.

Abstract

Probiotics can modulate the immune system, conferring beneficial effects on the host. Understanding how these microorganisms contribute to improve the health status is still a challenge. Previously, we have demonstrated that Enterococcus faecalis CECT7121 implants itself and persists in the murine gastrointestinal tract, and enhances and skews the profile of cytokines towards the Th1 phenotype in several biological models. Given the importance of dendritic cells (DCs) in the orchestration of immunity, the aim of this work was to elucidate the influence of E. faecalis CECT7121 on DCs and the outcome of the immune responses. In this work we show that E. faecalis CECT7121 induces a strong dose-dependent activation of DCs and secretion of high levels of IL-12, IL-6, TNFα, and IL-10. This stimulation is dependent on TLR signaling, and skews the activation of T cells towards the production of IFNγ. The influence of this activation in the establishment of Th responses in vivo shows the accumulation of specific IFNγ-producing cells. Our findings indicate that the activation exerted by E. faecalis CECT7121 on DCs and its consequence on the cellular adaptive immune response may have broad therapeutic implications in immunomodulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology*
  • Enterococcus faecalis / immunology*
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / microbiology
  • Immunity / drug effects
  • Immunity / immunology
  • Immunomodulation / drug effects*
  • Immunomodulation / immunology*
  • Interferon-gamma / immunology*
  • Interleukin-10 / immunology
  • Interleukin-12 / immunology
  • Interleukin-6 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Probiotics / administration & dosage*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma

Grant support

Our work was partly supported by University of Buenos Aires, Argentina (grant number 20020100101002) to MarAM and institutional funding from the Institute of Infection Immunology (Twincore, Hannover, Germany). This work was done in the frame of a scientific collaborative program (PROALAR DA/10/05) between the Institute of Infection Immunology (Twincore, Hannover, Germany) and the Laboratorio de Modulación de la Respuesta Inmune, (IDEHU,CONICET-UBA, Argentina) granted to TDS and MarAM by the Ministry of Science, Technology and Productive Innovation (MINCyT, Argentina) and the German Academic Exchange Service (DAAD, Germany). The funds granted by this program were exclusively aimed to cover the costs of travel and accommodations for travel between Germany and Argentina for the researchers involved to specific project tasks. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.