Toll-like receptor 3 is involved in airway epithelial cell response to nontypeable Haemophilus influenzae.
Nontypeable Haemophilus influenzae (NTHi) is the etiological agent most frequently associated with bacterial exacerbations of chronic obstructive pulmonary disease (COPD). The present work shows that NTHi strains induced in primary normal human bronchial epithelial cells (NHBE) a cytokine/chemokine response in which CCL-5 and CXCL-10 were predominant. Production of both cytokines was inhibited by an anti-TLR3 monoclonal antibody (mAb) in a dose-dependent manner, but not by control human IgG4 antibodies, thus suggesting a TLR3-dependency of the NTHi stimulation. BEAS-2B, an immortalized human bronchial epithelial cell line, also showed a similar NTHi-induced response that was inhibited by the anti-TLR3 mAb. A BEAS-2B cell line stably expressing TLR3 siRNA showed significantly reduced cytokine/chemokine responses to NTHi stimulation, confirming the role of TLR3 in the response. These results indicate that TLR3 is a key component in the response of human bronchial epithelial cells to NTHi, and suggest that cognate neutralizing mAbs might be a useful therapeutic tool to regulate the inflammatory response.
Teng
Fang
F
Department of Immunology, Centocor R&D Inc., Radnor, PA, United States. fteng@its.jnj.com
Slavik
Victoria
V
Duffy
Karen E
KE
San Mateo
Lani
L
Goldschmidt
Raul
R
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D034622:RNA Interference; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; C483024:CCL5 protein, human; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3