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Clinical and Vaccine Immunology, June 2009, p. 816-823, Vol. 16, No. 6
1071-412X/09/$08.00+0 doi:10.1128/CVI.00445-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Gene Expression of Nucleic Acid-Sensing Pattern Recognition Receptors in Children Hospitalized for Respiratory Syncytial Virus-Associated Acute Bronchiolitis
Carolina Scagnolari,1*
Fabio Midulla,2
Alessandra Pierangeli,1
Corrado Moretti,2
Enea Bonci,2
Rosaria Berardi,2
Daniela De Angelis,2
Carla Selvaggi,1
Paola Di Marco,1
Enrico Girardi,3 and
Guido Antonelli1
Department of Experimental Medicine, Virology Section, Sapienza University of Rome, Rome, Italy,1 Pediatric Department, Sapienza University of Rome, Rome, Italy,2 National Institute for Infectious Diseases L. Spallanzani, Rome, Italy3
Received 25 November 2008/ Returned for modification 9 January 2009/ Accepted 7 April 2009
Given the critical role of pattern recognition receptors (PRRs) in acid nucleic recognition in the initiation of innate immunity and the orchestration of adaptive immunity, the aim of this study was to determine whether any heterogeneity of PRR expression in the airway tracts of infants with respiratory syncytial virus (RSV) infection might explain the broad clinical spectrum of RSV-associated bronchiolitis in infants. For this purpose, the levels of melanoma differentiation-associated protein-5 (MDA-5), retinoic acid inducible gene-1 (RIG-1), and Toll-like receptor 3 (TLR-3), TLR-7, TLR-8, and TLR-9 mRNAs were evaluated, using TaqMan quantitative reverse transcription-PCR, in cells from nasopharyngeal washes collected from 157 infants suffering from acute bronchiolitis whether or not they were associated with respiratory viruses. High interindividual variability was observed in both virus-positive and -negative infants; however, the relative gene expression levels of MDA-5, RIG-1, TLR-7, and TLR-8 were significantly higher in the virus-infected group, whereas the expression levels of TLR-3 and TLR-9 were not significantly different. The differences in the gene expression of MDA-5, RIG-1, TLR-7, and TLR-8 were more evident in infants with RSV infection than in those with bocavirus or rhinovirus infection. In RSV-infected infants, PRR-mRNA levels also were analyzed in relation to interferon protein levels, viral load, clinical severity, days of hospitalization, age, and body weight. A significant positive correlation was observed only between RSV viral load and RIG-1 mRNA levels. These findings provide the first direct evidence that, in infants with respiratory virus-associated bronchiolitis, especially RSV, there are substantial changes in PRR gene expression; this likely is an important determinant of the clinical outcome of bronchiolitis.
* Corresponding author. Mailing address: Department of Experimental Medicine, Virology Section, Sapienza University of Rome, Viale di Porta Tiburtina 28, 00185 Rome, Italy. Phone: 39-06-4474246. Fax: 39-06-44741236. E-mail: carolina.scagnolari{at}uniroma1.it
Published ahead of print on 22 April 2009.
Clinical and Vaccine Immunology, June 2009, p. 816-823, Vol. 16, No. 6
1071-412X/09/$08.00+0 doi:10.1128/CVI.00445-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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