Commensal bacteria–derived signals regulate basophil hematopoiesis and allergic inflammation

Abstract

Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (TH2) cytokine–dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we identify that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum immunoglobulin E (IgE) levels, increased steady–state circulating basophil populations, and exaggerated basophil–mediated TH2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell–intrinsic expression of MyD88 was required to limit serum IgE levels and circulating basophil populations in mice. Commensal–derived signals were found to influence basophil development by limiting proliferation of bone marrow–resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal–derived signals influence basophil hematopoiesis and susceptibility to TH2 cytokine–dependent inflammation and allergic disease.

IgD class switching is initiated by microbiota and limited to mucosa-associated lymphoid tissue in mice

“…As expected for GF conditions (16,17), serum IgE was elevated in GF-WT mice compared with CNV.WT mice, and 53BP1 deficiency suppressed this elevation (Fig. S6), consistent with the absence of cCSR in 53BP1-deficient mice.…”

A Brave New World: The Lung Microbiota in an Era of Change

“…In a murine model of allergic airway disease, germ-free mice exhibit more severe disease than conventionally housed controls, an effect that could be ameliorated by recolonization with conventional microbiota (57). Similar results were found when disturbance of the gut microbiome was induced by administration of antibiotics in drinking water or by an antibiotic-fungal microbiota combination (42,58). Microbial colonization early in life regulates mucosal invariant natural killer T-cell tolerance and can impact immune responses at mucosal sites later in adulthood (59).…”

Investigating a holobiont: Microbiota perturbations and transkingdom networks

“…One protocol using a cocktail of 4 antibiotics for 4-5 weeks has been exceptionally popular among investigators and allowed to demonstrate the involvement of microbiota in host functions and disease pathogenesis in a variety of models. [29][30][31][32] Furthermore, a few studies compared both germfree and antibiotic-treated animals and detected concordant results. 31,33 However, concordant results are not always observed between these 2 models.…”

“…[29][30][31][32] Furthermore, a few studies compared both germfree and antibiotic-treated animals and detected concordant results. 31,33 However, concordant results are not always observed between these 2 models. For example, in an animal model of common variable immunodeficiency (CVID) associated enteropathy (in B lymphocyte deficient mice), we found that derivation of B cell knockout (BcKO) and control mice as germfree abolished differences in the host phenotype between the 2 genotypes observed in conventional mice ( Fig.…”