Respiratory Syncytial Virus Induces Pneumonia, Cytokine Response, Airway Obstruction, and Chronic Inflammatory Infiltrates Associated with Long‐Term Airway Hyperresponsiveness in Mice

Jafri, Hasan S.; Chávez-Bueno, Susana; Mejías, Asunción; Gómez, Ana M.; Ríos, Ana María; Nassi, Shahryar S.; Yusuf, Munira; Kapur, Payal; Hardy, R. Doug; Hatfield, Jeanine; Rogers, Beverly Barton; Krisher, Karen; Ramilo, Octavio

doi:10.1086/386372

Cited by 160 publications

(213 citation statements)

References 45 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…RSV infection of BALB/c mice represents a well-established experimental model, which has successfully been used to study the immunopathogenesis of RSV [23][24][25]. Lymphocytic response on day 5 post-infection and elevated levels of TNF-a, IL-6, KC and viral loads characterised RSV-infection in our study, consist with literature findings.…”

Section: Discussionsupporting

confidence: 87%

Host response to mechanical ventilation for viral respiratory tract infection

et al. 2012

View full text Add to dashboard Cite

Respiratory syncytial virus (RSV) bronchiolitis causes severe respiratory tract infection in infants, frequently necessitating mechanical ventilatory support. However, life-saving, mechanical ventilation aggravates lung inflammation. We set up a model to dissect the host molecular response to mechanical ventilation in RSV infection. Furthermore, the response to induced hypercapnic acidosis, reported to dampen the inflammatory response to mechanical ventilation in non-infectious models, was assessed.BALB/c mice were inoculated with RSV or mock-suspension and ventilated for 5 h on day 5 post inoculation.Mechanical ventilation of infected mice resulted in enhanced cellular influx and increased concentrations of pro-inflammatory cytokines in the bronchoalveolar space. Microarray analysis showed that enhanced inflammation was associated with a molecular signature of a stress response to mechanical ventilation with little effect on the virus-induced innate immune response. Hypercapnic acidosis during mechanical ventilation of infected mice did not change host transcript profiles.We conclude that mechanical ventilation during RSV infection adds a robust but distinct molecular stress response to virus-induced innate immunity activation, emphasising the importance of lung-protective mechanical ventilation strategies. Induced hypercapnic acidosis has no major effect on host transcription profiles during mechanical ventilation for RSV infection, suggesting that this is a safe approach to minimise ventilator-induced lung injury.KEYWORDS: Gene expression profiles, hypercapnic acidosis, mice, respiratory syncytial virus, ventilator-induced lung injury R espiratory syncytial virus (RSV) is the most common cause of seasonal acute respiratory tract illness of all ages [1,2]. More than 50% of all infants are infected with RSV during the first yr of life and by the age of 2 yrs almost all children have been infected [3]. Of these children ,1-2% will need hospitalisation and ,10% of these hospitalised children (,0.1% of all children) will require mechanical ventilation for a severe RSV infection during their first yr of life [4]. Hence, RSV infection is the most frequent cause of non-elective paediatric intensive care unit (PICU) admission for mechanical ventilatory support in infants during the winter season [5]. RSV pathogenesis is not completely understood. In humans, severe RSV infection results in a predominantly neutrophil infiltrate in bronchoalveolar lavage fluid (BALF) [6] and a strong innate pro-inflammatory response, reflected by exhaustion of the peripheral blood neutrophil pool after peak values of viral load and disease severity [7]. In mice, the innate immune response is characterised by induction of type I interferon (IFN)-regulated genes and chemokine genes, and genes involved in inflammation and antigen processing [8].Although life-saving, mechanical ventilation may induce or aggravate pulmonary inflammation and lung injury. Ventilator-induced lung injury (VILI) results from relatively high tidal volumes...

show abstract

Section: Discussionsupporting

confidence: 87%

Host response to mechanical ventilation for viral respiratory tract infection

et al. 2012

View full text Add to dashboard Cite

show abstract

“…We and others have previously shown that RSV infection induces AHR in response to methacholine challenge (18,23,28). As shown in Figure 3C, we observed a significant difference between RSV-and RSV ϩ BHA-treated animals, because administration of BHA strongly attenuated RSV-induced AHR at all methacholine doses.…”

Section: Bha Attenuates Rsv-induced Clinical Illnesssupporting

confidence: 72%

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Castro

Guerrero-Plata

Suarez-Real

et al. 2006

Am J Respir Crit Care Med

145

154

View full text Add to dashboard Cite

“…Our results proved that mice infected with RSV before sensitization to OVA had higher AHR than non-RSV-infected mice, but other asthmatic parameters and the level of IFN-␥, IL-4, and IL-10 in BALF were not significantly different. In our previous study, we found that the concentration of IFN-␥ but not IL-4 and IL-10 increased in BALF on d 7 postinfection from mice infected with RSV as compared with noninfected controls (data not shown), which was consistent with other findings (33,35) and could be explained as acute RSV infection resulting in a Th1-type cytokine response. However, in our present experimental system, augmentation of allergeninduced AHR after RSV infection could not be explained by a Th1/Th2 mechanism.…”

Section: Discussionsupporting

confidence: 90%

Respiratory Syncytial Virus Infection Reversed Anti-Asthma Effect of Neonatal Bacillus Calmette-Guerin Vaccination in BALB/c Mice

Yang

Wang

et al. 2006

Pediatr Res

View full text Add to dashboard Cite

Bacillus Calmette-Guerin (BCG) vaccination can protect animals from asthma, but the effect of BCG on childhood asthma prevention is controversial in humans. To verify the hypothesis that the BCG anti-asthma effect in childhood might be reversed by a respiratory virus infection, newborn BALB/c mice were divided into five groups. Control and ovalbumin (OVA) groups were mock vaccinated and mock infected. The BCG/OVA group was BCG vaccinated and mock infected. The respiratory syncytial virus (RSV)/ OVA group was mock vaccinated and RSV infected. The BCG/RSV/ OVA group was BCG vaccinated and RSV infected. Except for the control group, all groups underwent OVA sensitization and challenge. Airway hyperresponsiveness (AHR) was measured after challenge and cells in bronchoalveolar lavage fluid (BALF) were counted. Cytokines in BALF and serum OVA-specific IgE were detected by ELISA and inflammatory characteristics of lung sections were scored. Mice with neonatal BCG vaccination (BCG/OVA group) were significantly protected from BALF eosinophilia, AHR to methacholine, peribronchiolitis, alveolitis, and peribronchial eosinophilia in comparison with the OVA, RSV/OVA, and BCG/RSV/ OVA groups. AHR in the OVA group was greater than in the BCG/OVA group but lower than in the RSV/OVA and BCG/RSV/ OVA groups. No significant differences in BALF eosinophilia, AHR, and lung inflammation were found between the RSV/OVA and BCG/RSV/OVA groups. The impact of BCG vaccination on antiasthma in mice was not dependent on interferon-␥, IL-4, and IL-10 levels. The results suggested that RSV infection can reverse the anti-asthma effect of neonatal BCG vaccination in BALB/c mice.

show abstract

Respiratory Syncytial Virus Induces Pneumonia, Cytokine Response, Airway Obstruction, and Chronic Inflammatory Infiltrates Associated with Long‐Term Airway Hyperresponsiveness in Mice

Abstract: This model provides a means to investigate the immunopathogenesis of RSV infection and its association with reactive airway disease.

Cited by 160 publications

References 45 publications

Host response to mechanical ventilation for viral respiratory tract infection

Host response to mechanical ventilation for viral respiratory tract infection

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Respiratory Syncytial Virus Infection Reversed Anti-Asthma Effect of Neonatal Bacillus Calmette-Guerin Vaccination in BALB/c Mice

Contact Info

Product

Resources

About