Intestinal Microbial Diversity During Early-Life Colonization Shapes Long-Term IgE Levels

Cell Host Microbe. 2013 Nov 13;14(5):559-70. doi: 10.1016/j.chom.2013.10.004.

Abstract

Microbial exposure following birth profoundly impacts mammalian immune system development. Microbiota alterations are associated with increased incidence of allergic and autoimmune disorders with elevated serum IgE as a hallmark. The previously reported abnormally high serum IgE levels in germ-free mice suggests that immunoregulatory signals from microbiota are required to control basal IgE levels. We report that germ-free mice and those with low-diversity microbiota develop elevated serum IgE levels in early life. B cells in neonatal germ-free mice undergo isotype switching to IgE at mucosal sites in a CD4 T-cell- and IL-4-dependent manner. A critical level of microbial diversity following birth is required in order to inhibit IgE induction. Elevated IgE levels in germ-free mice lead to increased mast-cell-surface-bound IgE and exaggerated oral-induced systemic anaphylaxis. Thus, appropriate intestinal microbial stimuli during early life are critical for inducing an immunoregulatory network that protects from induction of IgE at mucosal sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • B-Lymphocytes / immunology
  • Biodiversity*
  • CD4-Positive T-Lymphocytes / immunology
  • Gastrointestinal Tract / microbiology*
  • Germ-Free Life
  • Immunoglobulin E / blood*
  • Interleukin-4 / immunology
  • Mice

Substances

  • Interleukin-4
  • Immunoglobulin E