Lipoprotein I, a TLR2/4 ligand modulates Th2-driven allergic immune responses.

Abstract

Asthma is an inflammatory lung disease that is initiated and directed by Th2 and inhibited by Th1 cytokines. Microbial infections have been shown to prevent allergic responses by inducing the secretion of the Th1 cytokines IL-12 and IFN-gamma. In this study, we examined whether administration of lipoprotein I (OprI) from Pseudomonas aeruginosa could prevent the inflammatory and physiological manifestations of asthma in a murine model of OVA-induced allergic asthma. OprI triggered dendritic cells to make IL-12 and TNF-alpha, with subsequent IFN-gamma production from T cells. OprI stimulation of dendritic cells involved both TLR2 and TLR4. Intranasal coadministration of OprI with OVA allergen resulted in a significant decrease in airway eosinophilia and Th2 (IL-4 and IL-13) cytokines and this effect was sustained after repeated allergen challenge. The immediate suppressive effect of OprI (within 2 days of administration) was accompanied by an increase in Th1 cytokine IFN-gamma production and a significant, but transient infiltration of neutrophils. OprI did not redirect the immune system toward a Th1 response since no increased activation of locally recruited Th1 cells could be observed upon repeated challenge with allergen. Our data show for the first time that a bacterial lipoprotein can modulate allergen-specific Th2 effector cells in an allergic response in vivo for a prolonged period via stimulation of the TLR2/4 signaling pathway.

• Authors: Hilde Revets, Gwenda Pynaert, Johan Grooten, Patrick De Baetselier
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 174 Issue 2 Pg. 1097-103 (Jan 15 2005) ISSN: 0022-1767 [Print] United States
• PMID: 15634935 (Publication Type: Journal Article)

Chemical References

• Allergens
• Bacterial Proteins
• Chemokines, CC
• Chemokines, CXC
• Cytokines
• Epitopes, T-Lymphocyte
• Ligands
• Lipoproteins
• Receptors, Cell Surface
• Tlr2 protein, mouse
• Tlr4 protein, mouse
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• outer membrane lipoprotein I, Bacteria
• Ovalbumin

Topics

• Administration, Intranasal
• Allergens (administration & dosage)
• Animals
• Antigen-Presenting Cells (immunology, metabolism)
• Bacterial Proteins (administration & dosage, metabolism, physiology)
• Cell Differentiation (immunology)
• Cells, Cultured
• Chemokines, CC (biosynthesis, physiology)
• Chemokines, CXC (biosynthesis, physiology)
• Cytokines (antagonists & inhibitors, biosynthesis)
• Dendritic Cells (cytology, immunology, metabolism)
• Eosinophilia (immunology, prevention & control)
• Epitopes, T-Lymphocyte (immunology)
• Ligands
• Lipoproteins (administration & dosage, metabolism, physiology)
• Lung (immunology, pathology)
• Mice
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophil Infiltration (immunology)
• Ovalbumin (immunology)
• Receptors, Cell Surface (deficiency, genetics, metabolism, physiology)
• Respiratory Hypersensitivity (immunology, prevention & control)
• T-Lymphocytes (immunology)
• Th2 Cells (immunology, metabolism)
• Toll-Like Receptor 2
• Toll-Like Receptor 4