Intestinal microbial diversity during early-life colonization shapes long-term IgE levels.
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.
Maurice Müller Laboratories (DKF), Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, Murtenstrasse 35, University of Bern, 3010 Bern, Switzerland.
Julia
J
Cahenzli
Yasmin
Y
Köller
Madeleine
M
Wyss
Markus B
MB
Geuking
Kathy D
KD
McCoy
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000276:immunology; D044822:Biodiversity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D007073:Immunoglobulin E / Q000097:blood*; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice
D015847:Interleukin-4; D007073:Immunoglobulin E