title: 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 (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.
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Hill
authors.forename: Mark C
authors.initials: MC
authors.lastname: Siracusa
authors.forename: Michael C
authors.initials: MC
authors.lastname: Abt
authors.forename: Brian S
authors.initials: BS
authors.lastname: Kim
authors.forename: Dmytro
authors.initials: D
authors.lastname: Kobuley
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.forename: Taku
authors.initials: T
authors.lastname: Kambayashi
authors.forename: David F
authors.initials: DF
authors.lastname: Larosa
authors.forename: Ellen D
authors.initials: ED
authors.lastname: Renner
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.forename: David
authors.initials: D
authors.lastname: Artis
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000906:Antibodies / Q000627:therapeutic use; D015703:Antigens, CD / Q000378:metabolism; D001491:Basophils / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000906:Antibodies; D015703:Antigens, CD; D016207:Cytokines; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D007073:Immunoglobulin E