Cahenzli, Julia; Köller, Yasmin; Wyss, Madeleine; Geuking, Markus; McCoy, Kathleen (2013). Intestinal Microbial Diversity during Early-Life Colonization Shapes Long-Term IgE Levels. Cell host & microbe, 14(5), pp. 559-570. Cell Press 10.1016/j.chom.2013.10.004
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Intestinal Microbial Diversity.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Open Access funded by European Research Council Download (1MB) | Preview |
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.
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