Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation

Nat Med. 2012 Mar 25;18(4):538-46. doi: 10.1038/nm.2657.


Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (T(H)2) cytokine-dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we find that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum IgE concentrations, increased steady-state circulating basophil populations and exaggerated basophil-mediated T(H)2 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 myeloid differentiation factor 88 (MyD88) was required to limit serum IgE concentrations 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 T(H)2 cytokine-dependent inflammation and allergic disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Antibodies / therapeutic use
  • Antigens, CD / metabolism
  • Basophils / cytology*
  • Basophils / drug effects*
  • Basophils / metabolism
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Guanine Nucleotide Exchange Factors / genetics
  • Hematopoiesis / drug effects*
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / genetics
  • Hypersensitivity / immunology*
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Inflammation / drug therapy
  • Inflammation / immunology*
  • Lymph Nodes / cytology
  • Mice
  • Myeloid Differentiation Factor 88 / metabolism
  • Signal Transduction / immunology
  • Th2 Cells / drug effects


  • Anti-Bacterial Agents
  • Antibodies
  • Antigens, CD
  • Cytokines
  • DOCK8 protein, human
  • Guanine Nucleotide Exchange Factors
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Immunoglobulin E