Pathogen recognition receptor crosstalk in respiratory syncytial virus sensing: a host and cell type perspective

Marr, Nico; Turvey, Stuart E.; Grandvaux, Nathalie

doi:10.1016/j.tim.2013.08.006

Cited by 28 publications

(28 citation statements)

References 59 publications

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“…Neonatal DCs from mice and humans, however, demonstrate limitations in markers of maturation such as cytokine production and co-stimulatory molecule expression upon TLR stimulation compared with adult DCs (44–47). Several PRRs including TLR2, TLR3, TLR4, TLR7, NOD2, RIG-I and MDA5 have been implicated in sensing RSV yet none conclusively (48–52). Less protective responses have been associated with genetic polymorphisms of TLR4 in some infant populations suggesting a role for sufficient TLR4 signaling in pathogenesis of disease (30).…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus–Specific CD8+ T Cell Immunodominance Hierarchy in Neonates

Malloy

Ruckwardt

Morabito

et al. 2017

The Journal of Immunology

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Young infants are generally more susceptible to viral infections and experience more severe disease than adults. CD8+ T cells are important for viral clearance and although often ineffective in neonates can be protective if adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8+ T cell immunodominance hierarchy to two RSV-derived epitopes, KdM282–90, and DbM187–195, was determined by the age at infection. To determine if age-dependent RSV specific CD8+ T cell responses could be modified through enhanced innate signaling, we used toll-like receptor (TLR) agonist 4 or 9 treatment at the time of infection, which remarkably changed the neonatal codominant response to an adult-like KdM282–90 CD8+ T cell immunodominant response. This shift was associated with an increase in the number of conventional dendritic cells (cDCs), CD11b+ and CD103+ DCs, in the lung-draining lymph node, and increased expression of the co-stimulatory molecule CD86. The magnitude of the KdM282–90 CD8+ T cell response in TLR-treated neonates could be blocked with antibodies against CD80 and CD86. These studies demonstrate the age-dependent function of cDCs, their role in determining immunodominance hierarchy, and epitope-specific CD8+ T cell requirements for co-stimulation that all influence the immune response magnitude. The unique impact of TLR agonists on neonatal T cell responses is important to consider for RSV vaccines designed for young infants.

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Section: Discussionmentioning

confidence: 99%

Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus–Specific CD8+ T Cell Immunodominance Hierarchy in Neonates

Malloy

Ruckwardt

Morabito

et al. 2017

The Journal of Immunology

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“…Further studies are needed to clarify ligand accessibility during the RSV life cycle, particularly in the context of innate immune recognition of RSV by DCs and alveolar macrophages (for a more comprehensive discussion, see our recent review article, Ref. 43). Moreover, diverging results may also be due to species-specific differences.…”

Section: Discussionmentioning

confidence: 99%

Attenuation of Respiratory Syncytial Virus–Induced and RIG-I–Dependent Type I IFN Responses in Human Neonates and Very Young Children

Marr

Wang

Kam

et al. 2014

The Journal of Immunology

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101

105

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Newborn infants, including those born at term without congenital disorders, are at high risk of severe disease from respiratory syncytial virus (RSV) infection. Indeed, our current local surveillance data demonstrate that approximately half of children hospitalized with RSV were ≤3 mo old, and 74% were born at term. Informed by this clinical epidemiology, we investigated antiviral innate immune responses in early life, with the goal of identifying immunological factors underlying the susceptibility of infants and young children to severe viral lower respiratory tract infections. We compared RSV-induced innate cytokine production in blood mononuclear cells from neonates, young children aged 12–59 mo, and healthy adults. RSV-induced IFN-α production was primarily mediated by plasmacytoid dendritic cells (pDCs), and was significantly lower in term infants and young children < 5 y of age than in adults (p < 0.01). RSV-induced IFN-α production in human pDCs proceeded independently of endosomal TLRs, and human pDCs from healthy adult donors produced IFN-α in a retinoic acid–inducible gene I protein (RIG-I)–dependent manner. Of interest, young age and premature birth were independently associated with attenuated RIG-I–dependent IFN-α responses (p < 0.01). In contrast to IFN-α production, proinflammatory IL-6 responses to RSV were mediated by monocytes, appeared less dependent on RIG-I, and were significantly impaired only among preterm infants, not in term infants and young children. Our results suggest that human pDCs are less functional in early life, which may contribute to the increased susceptibility of infants and young children to severe RSV disease.

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“…Several Toll-like receptors (TLRs), such as TLR2, 3, 4, and 7, are also implicated in the recognition of RSV 54, 55 . For example, RSV F can bind TLR4 56 and SNPs in the TLR4 gene correlate with severe RSV disease 57– 59 .…”

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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Pathogen recognition receptor crosstalk in respiratory syncytial virus sensing: a host and cell type perspective

Cited by 28 publications

References 59 publications

Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus–Specific CD8+ T Cell Immunodominance Hierarchy in Neonates

Pulmonary Dendritic Cell Subsets Shape the Respiratory Syncytial Virus–Specific CD8+ T Cell Immunodominance Hierarchy in Neonates

Attenuation of Respiratory Syncytial Virus–Induced and RIG-I–Dependent Type I IFN Responses in Human Neonates and Very Young Children

Respiratory syncytial virus infection: an innate perspective

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