Expression and Function of Toll-Like Receptors in Human Basophils

We investigated the expression and function of a panel of Toll-like receptors (TLRs) in human basophils. Basophil preparations constitutively expressed TLR2, TLR4, TLR9 and TLR10 mRNAs (TLR4 > TLR2 >> TLR9, TLR10). Although TLR mRNA expression in basophils was generally less prominent compared with those in neutrophils and monocytes, basophils expressed significantly higher levels of TLR2 and TLR4 mRNA than eosinophils. Various TLR ligands (Pam3Cys-Ser-Lys4, poly I:C, lipopolysaccharide, R-848, CpG DNA) were tested, but none affected the expression level of adhesion molecule CD11b or the viability of freshly purified basophils. On the other hand, when basophils were pretreated with interferon-γ before stimulation with TLR ligands, only the TLR4 ligand, lipopolysaccharide, upregulated CD11b expression. However, the surface levels of TLR2 and TLR4 on the interferon-γ-treated basophils showed no obvious changes. These results suggest that TLR4 on basophils may be involved in the pathogenesis of infection-induced exacerbation of allergic inflammation by modulating basophil functions.

[1]  J. Schroeder,et al.  Toll-like receptor 2 ligands activate human basophils for both IgE-dependent and IgE-independent secretion. , 2005, The Journal of allergy and clinical immunology.

[2]  R. Modlin.  Mammalian toll-like receptors. , 2002, Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology.

[3]  S. Dower,et al.  Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses1 , 2002, The Journal of Immunology.

[4]  T. Giese,et al.  Quantitative Expression of Toll-Like Receptor 1–10 mRNA in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and Sensitivity to CpG Oligodeoxynucleotides1 , 2002, The Journal of Immunology.

[5]  Kazuhiko Yamamoto,et al.  Cytokine‐mediated regulation of CXCR4 expression in human neutrophils , 2002, Journal of leukocyte biology.

[6]  W. Busse,et al.  Relationship of viral infections to wheezing illnesses and asthma , 2002, Nature Reviews Immunology.

[7]  O. Kawanami,et al.  Glucocorticoids induce basophil apoptosis. , 2001, The Journal of allergy and clinical immunology.

[8]  Kazuhiko Yamamoto,et al.  Expression of CXCR4 in Eosinophils: Functional Analyses and Cytokine-Mediated Regulation1 , 2000, The Journal of Immunology.

[9]  P. O'Byrne,et al.  Increased numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atopic asthmatics. , 2000, American journal of respiratory and critical care medicine.

[10]  P. Askenase,et al.  C-C chemokines in allergen-induced late-phase cutaneous responses in atopic subjects: association of eotaxin with early 6-hour eosinophils, and of eotaxin-2 and monocyte chemoattractant protein-4 with the later 24-hour tissue eosinophilia, and relationship to basophils and other C-C chemokines (mono , 1999, Journal of immunology.

[11]  K. Matsushima,et al.  Expression and regulation of monocyte chemoattractant protein‐1 by human eosinophils , 1997, European journal of immunology.

[12]  S. Galli,et al.  Identification of IgE-bearing cells in the late-phase response to antigen in the lung as basophils. , 1994, American journal of respiratory cell and molecular biology.

[13]  W. Busse,et al.  Respiratory infections and asthma. , 1992, The Medical clinics of North America.

[14]  R. Naclerio,et al.  Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils. , 1992, Journal of immunology.

[15]  S. Dower,et al.  Toll-Like Receptor (TLR)2 and TLR4 in Human Peripheral Blood Granulocytes: A Critical Role for Monocytes in Leukocyte Lipopolysaccharide Responses , 2002 .