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

Julia C., Yasmin Kr, Madeleine W., Markus B. G. and Kathy D. M. Cell.

 Host & Microbes. 2013. Vol. 14, 559-570.

Speaker: Wei-Lin Chen (陳薇稜)                                Time: 14:00~15:00, Oct. 8, 2014

Commentator: Jenn-Wei Chen (陳振暐 老師)            Room: Room 601

Abstract:

Microbiota profoundly impacts mammalian immune system development and we exposure in microbiota from neonate. When altered microbiota might result in the increasing incidence of allergic or autoimmune disease. Hyper IgE is the hallmark and a crucial role in atopic allergic disease. Normal IgE levels maintain in balance by immunoregulatory network regulates isotypeswitching to IgE. Those immunoregulatory network including T-B cell interaction and triggered B cell undergo isotype switching. In the previous study, abnormally high IgE level in Germ-free (GF) mice ^[1] suggest that immunoregulatory signals stemming from microbiota are essential for maintaining IgE on the basal level. Based on it, the authors’ postulate that microbiota plays a crucial role ofimmunoregulatory signals for IgE induction. To investigate this hypothesis, the author’s used GF mice and tested mouse total serum IgE. Then find that sterile mice IgE are higher than Specific Pathogen Free (SPF) mice (with normal microbial flora). Next, they tested B cell function of isotype switching to IgE and occurred in which lymphoid tissue producing in GF mice. The author’s detect eGerm-line transcript (eGLTs) gene expression, which gene is a hallmark of initial IgE production. The authors' found eGLT expressed on Peyer's patch (PP) and mesenteric lymph nodes (MLN), but not obviously detected it in spleen. The result suggest that IgE isotype switch to IgE at mucosal site in GF mice. Next, to determine B cell of GF mice undergo isotype switching whether require CD4⁺ T cell, MHC class II or cytokine Interleukin-4 (IL-4) to lead to develop hyper IgE ^[2]. Moreover, they use GF Rag1^-/- mice, which mice are immunodeficiency of B & T cell to identify.Experiments shows isotype switching to IgE dependent on CD4⁺ T cell and IL-4 manner, but not MHC class II or CD40. However, they identified whether microbiota involved in immune system development early in life and flora diversity regulates IgE production. They cohoused GF mice with SPF mice at several time point, such as time from birth (day 0) to adults (>8 week) and conventionalized GF mice with few to low-complexity species of intestinal microbiota. They found that only neonatal GF mice colonized with low-complexity microbiota can effectively inhibit hyperIgE development. Furthermore, they identify hyper IgE would alter mast-cell-mediated pathologies and observed that GF mice significantly increasing surface-bound IgE in peritoneal mast cells. Due to those evidences indicate immature immune system in GF mice might lead to exaggerated oral-induced systemic anaphylaxis. They induced mice developing anaphylaxis, found GF mice became more susceptibility to oral antigen-induced anaphylaxis. In summary, those results show that an appropriate intestinal microbial stimuli during early life are certainly for inducing animmunoregulatory network that can shape a long-term protection from induction IgE at mucosal site.

References:

1.  Herbst, T., et al. 2011. Dysregulation of allergic airway inflammation in the absence of microbial colonization. Am. J. Respir. Crit. Care Med. 184, 198-205.

2.  Bacharier, L.B., Geha, R.S. 2000. Molecular mechanisms of IgE regulation. J Allergy Clin Immunol. 105, S547-S558.