TLR3 in human eosinophils: functional effects and decreased expression during allergic rhinitis.

• BACKGROUND/AIM: Viral respiratory infections are increasingly implicated in allergic exacerbations. Virus-induced activation of eosinophils through Toll-like receptors (TLRs) could be involved. The present study was designed to examine TLR3 expression in eosinophils from bone marrow (BM) and peripheral blood (PB) during symptomatic allergic rhinitis, and to evaluate the functional responsiveness of TLR3 in purified eosinophils. METHODS: BM and PB samples were obtained from healthy volunteers and patients with seasonal allergic rhinitis outside and during the pollen season. Eosinophils were analyzed for TLR3 expression by flow cytometry. Polyinosinic:polycytidylic acid [poly(I:C)], an agonist for TLR3, was used to assess its functional role in purified eosinophils and the intracellular signaling pathways involved. RESULTS: TLR3 expression was demonstrated in BM and PB eosinophils. It was higher in BM-derived than in circulating cells and it was downregulated in both compartments during symptomatic allergic rhinitis. TLR3 expression was also downregulated in the presence of interleukin (IL)-4 and IL- 5. Stimulation with poly(I:C) increased the percentage of CD11b+ cells and enhanced the secretion of IL-8, effects mediated via the p38 mitogen-activated protein kinases and nuclear factor-kappaB signaling pathways. Moreover, pretreatment with IL-5 augmented the poly(I:C)-induced IL-8 release. CONCLUSIONS: Eosinophils activated via TLR3 might be more able to home and recruit leukocytes to sites of inflammation. The decreased TLR3 expression during symptomatic allergic rhinitis and in the presence of Th2 cytokines indicates a role in allergic airway inflammation. Thus, eosinophils might function as a link between viral infections and exacerbations of allergic disease.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)

Nyckelord

Adult

Antigens

CD11b

metabolism

Blood Cell Count

Bone Marrow Cells

cytology

Cell Count

Cysteine Proteinase Inhibitors

pharmacology

Eosinophils

cytology

drug effects

immunology

metabolism

Female

Gene Expression

genetics

Humans

Imidazoles

pharmacology

Interleukin-4

pharmacology

Interleukin-5

pharmacology

Interleukin-8

metabolism

Leupeptins

pharmacology

Male

Middle Aged

NF-kappa B

antagonists & inhibitors

metabolism

Neutrophils

metabolism

Phosphorylation

drug effects

Poly I-C

pharmacology

Protein Kinase Inhibitors

pharmacology

Pyridines

pharmacology

Rhinitis

Allergic

Seasonal

blood

immunology

metabolism

Signal Transduction

drug effects

physiology

Toll-Like Receptor 3

genetics

metabolism

Virus Diseases

immunology

Young Adult

p38 Mitogen-Activated Protein Kinases

antagonists & inhibitors

metabolism

Allergic rhinitis; Eosinophil; Adhesion molecule; Chemokine; Signal transduction; p38 MAP kinase; Nuclear factor-kappa B

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