Hill DA, Siracusa MC, Abt MA, Kim BS, Kobuley D, Kubo M, Kambayashi T, LaRosa DF, Renner ED, Orange JS, Bushman FD, Artis D, Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nat Med. 2011: 18:538-546. PMID: 22447074
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 basophilpopulations 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 influencebasophil hematopoiesis and susceptibility to T(H)2 cytokine-dependent inflammation and allergic disease.