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.
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Authors | M Arora, S L Poe, T B Oriss, N Krishnamoorthy, M Yarlagadda, S E Wenzel, T R Billiar, A Ray, P Ray |
Journal | Mucosal immunology
(Mucosal Immunol)
Vol. 3
Issue 6
Pg. 578-93
(Nov 2010)
ISSN: 1935-3456 [Electronic] United States |
PMID | 20664577
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibodies, Blocking
- Antigens, Differentiation
- CD11b Antigen
- Lipopolysaccharides
- Myeloid Differentiation Factor 88
- monocyte-macrophage differentiation antigen
- Interleukin-10
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Topics |
- Adoptive Transfer
- Animals
- Antibodies, Blocking
(administration & dosage)
- Antigens, Differentiation
(biosynthesis)
- CD11b Antigen
(biosynthesis)
- Cell Differentiation
(drug effects)
- Cell Movement
(drug effects)
- Cells, Cultured
- Eosinophilia
- Humans
- Hypersensitivity
(immunology, physiopathology, therapy)
- Immunosuppression Therapy
- Interleukin-10
(immunology)
- Lipopolysaccharides
(administration & dosage)
- Lung
(drug effects, immunology, metabolism, pathology)
- Mice
- Mice, Inbred BALB C
- Mice, Knockout
- Myeloid Cells
(drug effects, immunology, metabolism, pathology)
- Myeloid Differentiation Factor 88
(genetics, immunology, metabolism)
- Pyroglyphidae
(immunology)
- Th2 Cells
(drug effects, immunology, metabolism, pathology)
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