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Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation.

TitleCommensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation.
Publication TypeJournal Article
Year of Publication2012
AuthorsHill DA, Siracusa MC, Abt MC, Kim BS, Kobuley D, Kubo M, Kambayashi T, Larosa DF, Renner ED, Orange JS, Bushman FD, Artis D
JournalNat Med
Volume18
Issue4
Pagination538-46
Date Published2012 Apr
ISSN1546-170X
KeywordsAnimals, Anti-Bacterial Agents, Antibodies, Antigens, CD, Basophils, Bone Marrow Cells, Cells, Cultured, Cytokines, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Guanine Nucleotide Exchange Factors, Hematopoiesis, Humans, Hypersensitivity, Immunoglobulin E, Inflammation, Lymph Nodes, Mice, Myeloid Differentiation Factor 88, Signal Transduction, Th2 Cells
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.

DOI10.1038/nm.2657
Alternate JournalNat. Med.
PubMed ID22447074
PubMed Central IDPMC3321082
Grant List2-P30 CA016520 / CA / NCI NIH HHS / United States
AI061570 / AI / NIAID NIH HHS / United States
AI067946 / AI / NIAID NIH HHS / United States
AI074878 / AI / NIAID NIH HHS / United States
AI083480 / AI / NIAID NIH HHS / United States
AI087990 / AI / NIAID NIH HHS / United States
AI095466 / AI / NIAID NIH HHS / United States
AI095608 / AI / NIAID NIH HHS / United States
DK50306 / DK / NIDDK NIH HHS / United States
F32-AI085828 / AI / NIAID NIH HHS / United States
HL107589 / HL / NHLBI NIH HHS / United States
HL111501 / HL / NHLBI NIH HHS / United States
P30 AR057217 / AR / NIAMS NIH HHS / United States
R01 HL107589 / HL / NHLBI NIH HHS / United States
R01 HL111501 / HL / NHLBI NIH HHS / United States
T32 AI060516 / AI / NIAID NIH HHS / United States
T32 AI060516-05 / AI / NIAID NIH HHS / United States
T32-AI05528 / AI / NIAID NIH HHS / United States
T32-AI060516 / AI / NIAID NIH HHS / United States
UH2DK083981 / DK / NIDDK NIH HHS / United States

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