title: TLR4/MyD88-induced CD11b+Gr-1 int F4/80+ non-migratory myeloid cells suppress Th2 effector function in the lung.
abstract: In humans, environmental exposure to a high dose of lipopolysaccharide (LPS) protects from allergic asthma, the immunological underpinnings of which are not well understood. In mice, exposure to a high LPS dose blunted house dust mite-induced airway eosinophilia and T-helper 2 (Th2) cytokine production. Although adoptively transferred Th2 cells induced allergic airway inflammation in control mice, they were unable to do so in LPS-exposed mice. LPS promoted the development of a CD11b(+)Gr1(int)F4/80(+) lung-resident cell resembling myeloid-derived suppressor cells in a Toll-like receptor 4 and myeloid differentiation factor 88 (MyD88)-dependent manner that suppressed lung dendritic cell (DC)-mediated reactivation of primed Th2 cells. LPS effects switched from suppressive to stimulatory in MyD88(-/-) mice. Suppression of Th2 effector function was reversed by anti-interleukin-10 (IL-10) or inhibition of arginase 1. Lineage(neg) bone marrow progenitor cells could be induced by LPS to develop into CD11b(+)Gr1(int)F4/80(+)cells both in vivo and in vitro that when adoptively transferred suppressed allergen-induced airway inflammation in recipient mice. These data suggest that CD11b(+)Gr1(int)F4/80(+) cells contribute to the protective effects of LPS in allergic asthma by tempering Th2 effector function in the tissue.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: M
authors.initials: M
authors.lastname: Arora
authors.forename: S L
authors.initials: SL
authors.lastname: Poe
authors.forename: T B
authors.initials: TB
authors.lastname: Oriss
authors.forename: N
authors.initials: N
authors.lastname: Krishnamoorthy
authors.forename: M
authors.initials: M
authors.lastname: Yarlagadda
authors.forename: S E
authors.initials: SE
authors.lastname: Wenzel
authors.forename: T R
authors.initials: TR
authors.lastname: Billiar
authors.forename: A
authors.initials: A
authors.lastname: Ray
authors.forename: P
authors.initials: P
authors.lastname: Ray
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000943:Antigens, Differentiation / Q000096:biosynthesis; D039481:CD11b Antigen / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004802:Eosinophilia; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D019138:Antibodies, Blocking; D000943:Antigens, Differentiation; D039481:CD11b Antigen; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; C036763:monocyte-macrophage differentiation antigen; D016753:Interleukin-10