Abstract | BACKGROUND: Airborne microbial products have been reported to promote immune responses that suppress asthma, yet how these beneficial effects take place remains controversial and poorly understood. METHODS: We exposed mice to the bacterium Escherichia coli and subsequently induced allergic airway inflammation through sensitization and intranasal challenge with ovalbumin. RESULTS: Pulmonary exposure to the bacterium Escherichia coli leads to a suppression of allergic airway inflammation. This immune modulation was neither mediated by the induction of a T helper 1 (Th1) response nor regulatory T cells; however, it was dependent on Toll-like receptor 4 (TLR4) but did not involve TLR desensitisation. Dendritic cell migration to the draining lymph nodes and activation of T cells was unaffected by prior exposure to E. coli, while dendritic cells in the lung displayed a less activated phenotype and had impaired antigen presentation capacity. Consequently, in situ Th2 cytokine production was abrogated. The suppression of airway hyper-responsiveness was mediated through the recruitment of gd T cells; however, the suppression of dendritic cells and T cells was mediated through a distinct mechanism that could not be overcome by the local administration of activated dendritic cells, or by the in vivo administration of tumour necrosis factor a. CONCLUSION: Our data reveal a localized immunoregulatory pathway that acts to protect the airways from allergic inflammation.
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Authors | Chiara Nembrini, Anke Sichelstiel, Jan Kisielow, Michael Kurrer, Manfred Kopf, Benjamin J Marsland |
Journal | Thorax
(Thorax)
Vol. 66
Issue 9
Pg. 755-63
(Sep 2011)
ISSN: 1468-3296 [Electronic] England |
PMID | 21422039
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Bacterial Outer Membrane Proteins
- TLR protein, bacteria
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Topics |
- Animals
- Asthma
(immunology, pathology, prevention & control)
- Bacterial Outer Membrane Proteins
(immunology, metabolism)
- Bronchoalveolar Lavage Fluid
(cytology, immunology)
- Dendritic Cells
(immunology)
- Disease Models, Animal
- Escherichia coli
(immunology, isolation & purification, metabolism)
- Flow Cytometry
- Immunomodulation
(immunology)
- Mice
- Mice, Inbred BALB C
- Mice, Inbred C57BL
- Th2 Cells
(immunology)
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