title: H. influenzae potentiates airway epithelial cell responses to rhinovirus by increasing ICAM-1 and TLR3 expression.
abstract: Rhinovirus (RV) is an important trigger of chronic obstructive pulmonary disease (COPD) exacerbations. In addition, respiratory viruses are more likely to be isolated in patients with a history of frequent exacerbations, suggesting that these patients are more susceptible to viral infection. To examine potential mechanisms for cooperative effects between bacterial and viral infection in COPD, we studied the responses of cultured human airway epithelial cells to nontypeable Hemophilus influenzae and RV. In both 16HBE14o- and primary mucociliary-differentiated cells, preincubation with H. influenzae enhanced RV serotype 39-induced protein expression of interleukin (IL)-8, epithelial-derived neutrophil attractant-78, and growth-related oncogene-alpha. H. influenzae infection also increased the binding of RV39 to cultured cells, as well as expression of intercellular adhesion molecule (ICAM)-1 and Toll-like receptor (TLR)-3, receptors for RV and dsRNA, respectively. Neutralizing antibody against tumor necrosis factor-alpha inhibited IL-8 expression induced by H. influenzae and RV39. Finally, siRNA against TLR3 attenuated RV-induced IL-8 expression. We conclude that H. influenzae infection increases airway epithelial cell ICAM-1 and TLR3 expression, leading to enhanced binding of RV and a potentiation of RV-induced chemokine release. These data provide a cellular mechanism by which H. influenzae infection may increase the susceptibility of COPD patients to RV-induced exacerbations.
authors.affiliation: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Umadevi S
authors.initials: US
authors.lastname: Sajjan
authors.forename: Yue
authors.initials: Y
authors.lastname: Jia
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Newcomb
authors.forename: J Kelley
authors.initials: JK
authors.lastname: Bentley
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Lukacs
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D006193:Haemophilus influenzae / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D010850:Picornaviridae Infections / Q000209:etiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology; D011991:Receptors, Virus / Q000235:genetics; D012137:Respiratory System / Q000473:pathology / Q000821:virology*; D012229:Rhinovirus / Q000472:pathogenicity*; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D011991:Receptors, Virus; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D018799:Intercellular Adhesion Molecule-1