Elevated Levels of Type 2 Respiratory Innate Lymphoid Cells in Human Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Vu, Luan; Siefker, David; Jones, Tamekia L.; You, Dahui; Taylor, Ryleigh; DeVincenzo, John P.; Cormier, Stephania A.

doi:10.1164/rccm.201812-2366oc

Cited by 67 publications

(61 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A total of 58 infants hospitalized with RSV were enrolled in the study (Table 1). This work includes samples from 23 patients that were used in a study recently submitted for publication and 33 patients used in another study recently accepted for publication [43]. Inclusion criteria were patients less than 12 months old (1 control patient was 368 days old), informed consent from parent or guardian, patients could not have a positive blood culture within 72 h prior to collection of stool, patients could not be diagnosed with any immunodeficiency, patients could not be on any antibiotics within 4 weeks prior to enrollment, patients could not have been placed on oxygen for more than 7 days within 3 months prior to the study, patients could not be receiving other investigational immunomodulatory or investigational antiviral agents, patients could not have a hemodynamically significant congenital heart disease, and patients must have tested positive for RSV and negative for influenza, by RT-PCR or be positive for RSV antigens tested by the hospital's diagnostic lab.…”

Section: Patient Enrollment and Sample Collectionmentioning

confidence: 99%

Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

Harding

Siefker

et al. 2020

BMC Microbiol

Self Cite

View full text Add to dashboard Cite

Background: Respiratory syncytial virus (RSV) is the number one cause of lower respiratory tract infections in infants. There are still no vaccines or specific antiviral therapies against RSV, mainly due to the inadequate understanding of RSV pathogenesis. Recent data suggest a role for gut microbiota community structure in determining RSV disease severity. Our objective was to determine the gut microbial profile associated with severe RSV patients, which could be used to help identify at-risk patients and develop therapeutically protective microbial assemblages that may stimulate immuno-protection. Results: We enrolled 95 infants from Le Bonheur during the 2014 to 2016 RSV season. Of these, 37 were wellbabies and 58 were hospitalized with RSV. Of the RSV infected babies, 53 remained in the pediatric ward (moderate) and 5 were moved to the pediatric intensive care unit at a later date (severe). Stool samples were collected within 72 h of admission; and the composition of gut microbiota was evaluated via 16S sequencing of fecal DNA. There was a significant enrichment in S24_7, Clostridiales, Odoribacteraceae, Lactobacillaceae, and Actinomyces in RSV (moderate and severe) vs. controls. Patients with severe RSV disease had slightly lower alpha diversity (richness and evenness of the bacterial community) of the gut microbiota compared to patients with moderate RSV and healthy controls. Beta diversity (overall microbial composition) was significantly different between all RSV patients (moderate and severe) compared to controls and had significant microbial composition separating all three groups (control, moderate RSV, and severe RSV). Conclusions: Collectively, these data demonstrate that a unique gut microbial profile is associated with RSV disease and with severe RSV disease with admission to the pediatric intensive care unit. More mechanistic experiments are needed to determine whether the differences observed in gut microbiota are the cause or consequences of severe RSV disease.

show abstract

Section: Patient Enrollment and Sample Collectionmentioning

confidence: 99%

Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

Harding

Siefker

et al. 2020

BMC Microbiol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whether the cellular arm of the adaptive pulmonary response is detrimental or beneficial in RSV disease is still debated. Particularly, the contribution of IL-4 to viral clearance versus immunopathogenesis remains controversial (25,(45)(46)(47). Recently, a study performed in hospitalized infants showed a possible involvement of Tc2 cells in disease severity.…”

Section: Discussionmentioning

confidence: 99%

The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis

Démoulins

Brügger

Zumkehr

et al. 2020

Preprint

View full text Add to dashboard Cite

Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in infancy, potentially aided by an inappropriate immune response. Sparse information is available for the distal lung, mostly because data arose from non-invasive samplings of peripheral blood and nasal aspirates. Objectives: To determine the neonatal immune response to RSV in the bronchoalveolar space and better understand why neonates are at greater risk of developing severe disease. Methods: We used the newborn lamb, a state-of-the-art translational model of human RSV infection, offering ease sampling and full accessibility to lower airways. Using a multiparameter flow cytometry assay, we evaluated the frequency and activation/maturation state of the major subsets of the developing T-cell compartment. Measurements and Main Results: The T-cell compartment of the healthy developing lung was very distinct to that seen in adults. We observed a high frequency of type 2 CD4+ (Th2) and CD8+ (Tc2) T-cells, both being a large source of IL-4, which declined progressively over time. Remarkably, RSV infection exacerbated this pro-type 2 environment, rather than inducing a type 2 response per se. Neonatal regulatory T-cell (Treg) suppressive functions occurred very early to dampen those Th2 and Tc2 responses, while γδ T-cells dropped and failed to produce IL-17. The disease severity was related to the magnitude of these T-cell responses. Conclusion: The atypical neonatal immune response to RSV consists of distinct T-cell subsets that tightly cooperate, namely a combined bronchoalveolar influx of Treg, Th2 and Tc2 cells, associated with a depletion of γδ T-cells.

show abstract

“…In the context of viral bronchiolitis, it is important to mention that several studies have described that respiratory syncytial virus (RSV) and rhinovirus, the most common causes of bronchiolitis [36], are more likely to elicit Th2/type 2 airway responses and bronchial ASM hyperactivity in neonatal mice than in mature animals [35,37]. Similarly, studies in human infants have reported that early-life rhinovirus infections are associated with robust Th2/type 2 airway responses [38,39], and that RSV-infected infants with severe disease exhibit a Th2 polarisation in their respiratory secretions [40,41].…”

Section: β 2 -Ar Agonist Responsiveness and Virus-induced Type 2 Immumentioning

confidence: 99%

“…Respiratory viruses can promote Th2/type 2 responses during early life [35,[37][38][39][40][41], but the degree in which this occurs seems to be modified by the virus type. Studies suggest that rhinovirus-infected infants display a different acquired immunological response compared to infants with RSV bronchiolitis, with a stronger predominance of Th2 polarisation (Th2/Th1 ratios) [42].…”

Section: Causative Virus Viral Bronchiolitis Seasonality and Potentmentioning

confidence: 99%

The use of β₂-adrenoreceptor agonists in viral bronchiolitis: scientific rationale beyond evidence-based guidelines

2020

View full text Add to dashboard Cite

Despite scientific evidence proving that inhaled β2-adrenergic receptor (β2-AR) agonists can reverse bronchoconstriction in all ages, current guidelines advocate against the use of β2-AR bronchodilators in infants with viral bronchiolitis because clinical trials have not demonstrated an overall clinical benefit. However, there are many different types of viral bronchiolitis, with variations occurring at an individual and viral level. To discard a potentially helpful treatment from all children regardless of their clinical features may be unwarranted. Unfortunately, the clinical criteria to identify the infants that may benefit from bronchodilators from those who do not are not clear. Thus, we summarised the current understanding of the individual factors that may help clinicians determine the highest probability of response to β2-AR bronchodilators during viral bronchiolitis, based on the individual immunobiology, viral pathogen, host factors and clinical presentation.

show abstract

Elevated Levels of Type 2 Respiratory Innate Lymphoid Cells in Human Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Cited by 67 publications

References 47 publications

Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis

The use of β₂-adrenoreceptor agonists in viral bronchiolitis: scientific rationale beyond evidence-based guidelines

Contact Info

Product

Resources

About

Elevated Levels of Type 2 Respiratory Innate Lymphoid Cells in Human Infants with Severe Respiratory Syncytial Virus Bronchiolitis

Cited by 67 publications

References 47 publications

Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

Altered gut microbiota in infants is associated with respiratory syncytial virus disease severity

The specific features of the developing T cell compartment of the neonatal lung are a determinant of respiratory syncytial virus immunopathogenesis

The use of β2-adrenoreceptor agonists in viral bronchiolitis: scientific rationale beyond evidence-based guidelines

Contact Info

Product

Resources

About

The use of β₂-adrenoreceptor agonists in viral bronchiolitis: scientific rationale beyond evidence-based guidelines