Rhinovirus infection liberates planktonic bacteria from biofilm and increases chemokine responses in cystic fibrosis airway epithelial cells
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Chattoraj, Sangbrita S.
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Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Chattoraj, Sangbrita S.
[1
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Ganesan, Shyamala
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Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Ganesan, Shyamala
[1
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Jones, Andrew M.
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Univ S Manchester Hosp, NHS Trust Wythenshawe Hosp, Manchester Adult Cyst Fibrosis Ctr, Manchester M20 8LR, Lancs, EnglandUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Jones, Andrew M.
[2
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Helm, Jennifer M.
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Univ S Manchester Hosp, NHS Trust Wythenshawe Hosp, Manchester Adult Cyst Fibrosis Ctr, Manchester M20 8LR, Lancs, EnglandUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Helm, Jennifer M.
[2
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Comstock, Adam T.
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Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Comstock, Adam T.
[1
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Bright-Thomas, Rowland
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Univ S Manchester Hosp, NHS Trust Wythenshawe Hosp, Manchester Adult Cyst Fibrosis Ctr, Manchester M20 8LR, Lancs, EnglandUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Bright-Thomas, Rowland
[2
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LiPuma, John J.
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Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
LiPuma, John J.
[1
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Hershenson, Marc B.
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Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI USAUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Hershenson, Marc B.
[1
,3
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Sajjan, Umadevi S.
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Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
Sajjan, Umadevi S.
[1
]
机构:
[1] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA
[2] Univ S Manchester Hosp, NHS Trust Wythenshawe Hosp, Manchester Adult Cyst Fibrosis Ctr, Manchester M20 8LR, Lancs, England
[3] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI USA
Background Intermittent viral exacerbations in patients with cystic fibrosis (CF) with chronic Pseudomonas aeruginosa (PA) infection are associated with increased bacterial load. A few clinical studies suggest that rhinoviruses (RV) are associated with the majority of viral-related exacerbations in CF and require prolonged intravenous antibiotic treatment. These observations imply that acute RV infection may increase lower respiratory symptoms by increasing planktonic bacterial load. However, the underlying mechanisms are not known. Methods Primary CF airway epithelial cells differentiated into mucociliary phenotype were infected with mucoid PA (MPA) followed by RV and examined for bacterial density, biofilm mass, levels of chemokines and hydrogen peroxide (H2O2). The need for dual oxidase 2, a component of NADPH oxidase, in RV-induced generation of H2O2 in CF cells was assessed using gene-specific siRNA. Results Superinfection with RV increased chemokine responses in CF mucociliary-differentiated airway epithelial cells with pre-existing MPA infection in the form of biofilm. This was associated with the presence of planktonic bacteria at both the apical and basolateral epithelial cell surfaces. Further, RV-induced generation of H2O2 via dual oxidase 2 in CF cells was sufficient for dispersal of planktonic bacteria from the biofilm. Inhibition of NADPH oxidase reduced bacterial transmigration across mucociliary-differentiated CF cells and the interleukin-8 response in MPA- and RV-infected cells. Conclusion This study shows that acute infection with RV liberates planktonic bacteria from biofilm. Planktonic bacteria, which are more proinflammatory than their biofilm counterparts, stimulate increased chemokine responses in CF airway epithelial cells which, in turn, may contribute to the pathogenesis of CF exacerbations.