Rhinovirus infection liberates planktonic bacteria from biofilm and increases chemokine responses in cystic fibrosis airway epithelial cells

被引:65
作者
Chattoraj, Sangbrita S. [1 ]
Ganesan, Shyamala [1 ]
Jones, Andrew M. [2 ]
Helm, Jennifer M. [2 ]
Comstock, Adam T. [1 ]
Bright-Thomas, Rowland [2 ]
LiPuma, John J. [1 ]
Hershenson, Marc B. [1 ,3 ]
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
基金
美国国家卫生研究院;
关键词
NITRIC-OXIDE SYNTHASE; PSEUDOMONAS-AERUGINOSA; INDUCED DISPERSION; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; VIRAL-INFECTIONS; HOST-DEFENSE; IN-VITRO; EXACERBATIONS; EXPRESSION;
D O I
10.1136/thx.2010.151431
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
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.
引用
收藏
页码:333 / 339
页数:7
相关论文
共 36 条
  • [1] Adult cystic fibrosis exacerbations and new strains of Pseudomonas aeruginosa
    Aaron, SD
    Ramotar, K
    Ferris, W
    Vandemheen, K
    Saginur, R
    Tullis, E
    Haase, D
    Kottachchi, D
    St Denis, M
    Chan, F
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 169 (07) : 811 - 815
  • [2] Involvement of nitric oxide in biofilm dispersal of Pseudomonas aeruginosa
    Barraud, Nicolas
    Hassett, Daniel J.
    Hwang, Sung-Hei
    Rice, Scott A.
    Kjelleberg, Staffan
    Webb, Jeremy S.
    [J]. JOURNAL OF BACTERIOLOGY, 2006, 188 (21) : 7344 - 7353
  • [3] The role of oxidative stress in rhinovirus induced elaboration of IL-8 by respiratory epithelial cells
    Biagioli, MC
    Kaul, P
    Singh, I
    Turner, RB
    [J]. FREE RADICAL BIOLOGY AND MEDICINE, 1999, 26 (3-4) : 454 - 462
  • [4] The Calgary Biofilm Device: New technology for rapid determination of antibiotic susceptibilities of bacterial biofilms
    Ceri, H
    Olson, ME
    Stremick, C
    Read, RR
    Morck, D
    Buret, A
    [J]. JOURNAL OF CLINICAL MICROBIOLOGY, 1999, 37 (06) : 1771 - 1776
  • [5] Pseudomonas aeruginosa flagellin and alginate elicit very distinct gene expression patterns in airway epithelial cells:: Implications for cystic fibrosis disease
    Cobb, LM
    Mychaleckyj, JC
    Wozniak, DJ
    López-Boado, YS
    [J]. JOURNAL OF IMMUNOLOGY, 2004, 173 (09) : 5659 - 5670
  • [6] Effects of upper respiratory tract infections in patients with cystic fibrosis
    Collinson, J
    Nicholson, KG
    Cancio, E
    Ashman, J
    Ireland, DC
    Hammersley, V
    Kent, J
    OCallaghan, C
    [J]. THORAX, 1996, 51 (11) : 1115 - 1122
  • [7] Contoli M, 2009, MINERVA MED, V100, P467
  • [8] Rhinovirus C and Respiratory Exacerbations in Children with Cystic Fibrosis
    de Almeida, Marina B.
    Zerbinati, Rodrigo M.
    Tateno, Adriana F.
    Oliveira, Cristina M.
    Romao, Renata M.
    Rodrigues, Joaquim C.
    Pannuti, Claudio S.
    da Silva Filho, Luiz Vicente F.
    [J]. EMERGING INFECTIOUS DISEASES, 2010, 16 (06) : 996 - 999
  • [9] Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense
    Geiszt, M
    Witta, J
    Baffi, J
    Lekstrom, K
    Leto, TL
    [J]. FASEB JOURNAL, 2003, 17 (09) : 1502 - +
  • [10] Characterization of starvation-induced dispersion in Pseudomonas putida biofilms
    Gjermansen, M
    Ragas, P
    Sternberg, C
    Molin, S
    Tolker-Nielsen, T
    [J]. ENVIRONMENTAL MICROBIOLOGY, 2005, 7 (06) : 894 - 906