Elevated IL-3 and IL-12p40 levels in the lower airway of infants with RSV-induced bronchiolitis correlate with recurrent wheezing

Bertrand, P.; Lay, Margarita K.; Piedimonte, Giovanni; Brockmann, Pablo E.; Palavecino, Christian Erick; Hernández, Jury; León, Mónica; Kalergis, Alexis M.; Bueno, Susan M.

doi:10.1016/j.cyto.2015.07.017

Cited by 48 publications

(53 citation statements)

References 48 publications

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“…The monocytes are important for controlling the virus and have recently been shown to contribute to viral clearance/control of RSV in the lower airways of mice 24 . Interestingly, children with bronchiolitis display high levels of CCL2 in nasopharyngeal wash 50 and in bronchoalveolar lavage (BAL) fluid 75, 76 . In the mouse model of RSV infection, lung monocytes are anti-viral and contribute to host protection 24 , while in a model of influenza virus infection monocytes cause pathology 77, 78 .…”

Section: Innate Immune Responses To Rsvmentioning

confidence: 99%

Respiratory syncytial virus infection: an innate perspective

Johansson

2016

F1000Res

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Respiratory syncytial virus (RSV) is a common cause of upper respiratory tract infection in children and adults. However, infection with this virus sometimes leads to severe lower respiratory disease and is the major cause of infant hospitalisations in the developed world. Several risk factors such as baby prematurity and congenital heart disease are known to predispose towards severe disease but previously healthy, full-term infants can also develop bronchiolitis and viral pneumonia during RSV infection. The causes of severe disease are not fully understood but may include dysregulation of the immune response to the virus, resulting in excessive recruitment and activation of innate and adaptive immune cells that can cause damage. This review highlights recent discoveries on the balancing act of immune-mediated virus clearance versus immunopathology during RSV infection.

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Section: Innate Immune Responses To Rsvmentioning

confidence: 99%

Respiratory syncytial virus infection: an innate perspective

Johansson

2016

F1000Res

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“…Indeed, a lower efficiency of immature DCs and of T and B lymphocytes, with a Th2 polarization, may adversely affect the adaptive immune response to the first RSV‐induced bronchiolitis, but also lay the foundations for the increased susceptibility to subsequent respiratory infections . Elevated levels of Th2 cytokines and pro‐inflammatory cytokines and chemokines were detected in nasopharyngeal aspirates (NPA) and BAL fluid from infants hospitalized with RSV bronchiolitis and a direct correlation found between IL‐3 and IL‐12p40 levels and the development of recurrent wheezing later in life . Moreover, at the time of RSV bronchiolitis, the presence in nasal epithelia of increased levels of a Th2 cytokine (CCL5) involved in eosinophilic inflammation was associated with the increased likelihood of subsequent asthma .…”

Section: Possible Impact Of Viral and Host Factors On Subsequent Respmentioning

confidence: 99%

“…Nanoparticle vaccines include assemblies of synthesized polypeptides, presenting multiple copies of subunit antigens that can potentially mimic the size and shape of the natural antigenic virus‐encoded proteins. Phase I, II, and III clinical trials on RSV F nanoparticle vaccines, with or without adjuvants, are ongoing in adults, including healthy third‐trimester pregnant women . Subunit vaccines, based on purified proteins isolated from RSV that have an elevated capacity to induce neutralizing antibodies, are in different phase clinical trials . These include the purified F protein, the central conserved region of the RSV‐A G protein, a chimeric RSV F‐G fusion protein, the CX3C central conserved region of the G protein, a post‐fusion RSV F protein formulated with a synthetic TLR4 agonist, purified recombinant pre‐fusion F protein, and extracellular domain of the SH protein . Live‐attenuated RSV vaccines must be characterized by a sufficiently attenuated viral replication to be safe in RSV‐naive infants but not too attenuated to eliminate an effective immune response with an adequate balance between safety and efficacy.…”

Section: Current Antiviral Approaches For Rsv Infectionmentioning

confidence: 99%

Respiratory syncytial virus–Host interaction in the pathogenesis of bronchiolitis and its impact on respiratory morbidity in later life

Rossi

Colin

2017

Pediatric Allergy Immunology

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Respiratory syncytial virus (RSV) is the most common agent of severe airway disease in infants and young children. Large epidemiologic studies have demonstrated a clear relationship between RSV infection and subsequent recurrent wheezing and asthma into childhood, thought to be predominantly related to long-term changes in neuroimmune control of airway tone rather than to allergic sensitization. These changes appear to be governed by the severity of the first RSV infection in infancy which in term depends on viral characteristics and load, but perhaps as importantly, on the genetic susceptibility and on the constitutional characteristic of the host. A variety of viral and host factors and their interplay modify the efficiency of the response to infection, including viral replication and the magnitude of structural and functional damage to the respiratory structures, and ultimately the extent, severity, and duration of subsequent wheezing.

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“…Infection with hRSV produces pulmonary inflammatory hyperresponsiveness with significant lung damage due to a T helper 2 (Th2)-biased immune response in the susceptible [2]. Along these lines, elevated Th2 cytokines including IL-3, IL-4, IL-10 and IL-13 were found in the airways in infants with hRSV bronchiolitis [3]. Upon hRSV infection in mice, moderate bronchiolitis, reduced activity and weight loss is observed [4,5].…”

Section: Introductionmentioning

confidence: 99%

TCR Repertoire Characterization for T Cells Expanded in Response to hRSV Infection in Mice Immunized with a Recombinant BCG Vaccine

Rey-Jurado

Böhmwald

Correa

et al. 2020

Viruses

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T cells play an essential role in the immune response against the human respiratory syncytial virus (hRSV). It has been described that both CD4 + and CD8 + T cells can contribute to the clearance of the virus during an infection. However, for some individuals, such an immune response can lead to an exacerbated and detrimental inflammatory response with high recruitment of neutrophils to the lungs. The receptor of most T cells is a heterodimer consisting of α and β chains (αβTCR) that upon antigen engagement induces the activation of these cells. The αβTCR molecule displays a broad sequence diversity that defines the T cell repertoire of an individual. In our laboratory, a recombinant Bacille Calmette-Guérin (BCG) vaccine expressing the nucleoprotein (N) of hRSV (rBCG-N-hRSV) was developed. Such a vaccine induces T cells with a Th1 polarized phenotype that promote the clearance of hRSV infection without causing inflammatory lung damage. Importantly, as part of this work, the T cell receptor (TCR) repertoire of T cells expanded after hRSV infection in naïve and rBCG-N-hRSV-immunized mice was characterized. A more diverse TCR repertoire was observed in the lungs from rBCG-N-hRSV-immunized as compared to unimmunized hRSV-infected mice, suggesting that vaccination with the recombinant rBCG-N-hRSV vaccine triggers the expansion of T cell populations that recognize more viral epitopes. Furthermore, differential expansion of certain TCRVβ chains was found for hRSV infection (TCRVβ + 8.3 and TCRVβ + 5.1,5.2) as compared to rBCG-N-hRSV vaccination (TCRVβ + 11 and TCRVβ + 12). Our findings contribute to better understanding the T cell response during hRSV infection, as well as the functioning of a vaccine that induces a protective T cell immunity against this virus.

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Elevated IL-3 and IL-12p40 levels in the lower airway of infants with RSV-induced bronchiolitis correlate with recurrent wheezing

Cited by 48 publications

References 48 publications

Respiratory syncytial virus infection: an innate perspective

Respiratory syncytial virus infection: an innate perspective

Respiratory syncytial virus–Host interaction in the pathogenesis of bronchiolitis and its impact on respiratory morbidity in later life

TCR Repertoire Characterization for T Cells Expanded in Response to hRSV Infection in Mice Immunized with a Recombinant BCG Vaccine

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