Flt3 ligand improves the innate response to respiratory syncytial virus and limits lung disease upon RSV reexposure in neonate mice

Rémot, Aude; Descamps, Delphyne; Jouneau, Luc; Laubreton, Daphné; Dubuquoy, Catherine; Bouet, Stéphan; Lecardonnel, Jérôme; Rebours, Emmanuelle; Petit-Camurdan, Agnès; Riffault, Sabine

doi:10.1002/eji.201545929

Cited by 28 publications

(53 citation statements)

References 25 publications

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“…Activated IRF3 and IRF7 translocate to the nucleus to transactivate IFN-α and IFN-β gene expression. TLR3 activation in macrophages during RSV infection (Tsai et al, 2015) culminates in IFN-β expression/production, by virtue of IRF3 and IRF7 activation (Casola et al, 2001; Jewell et al, 2007; Sabbah et al, 2009; Remot et al, 2016). In that regard, IRF7 is required for IFN-β gene expression following TLR3 activation (Siednienko et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…IRF7 is a virus specific IFN-β inducer operating during MyD88-independent TLR signaling (e.g., TLR3 signaling) (Honda et al, 2005). RSV induces IRF7 expression in cells and mice respiratory tract (Casola et al, 2001; Jewell et al, 2007; Remot et al, 2016). Furthermore, IRF7 is constitutively expressed (and induced following virus infection) in primary macrophages and macrophage cell-lines like RAW 264.7 cells (Wilden et al, 2009; Ning et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Pokharel

Shil

Bose

2016

Front. Cell. Infect. Microbiol.

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Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children, and immuno-compromised individuals. RSV triggers transforming growth factor-β (TGF-β) production from lung epithelial cells and TGF-β facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-β and the role of TGF-β if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-β and as a consequence these cells activate TGF-β dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-β production from RSV infected macrophages. In an effort to elucidate the role of TGF-β and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-β—SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g., interferon-β or IFN-β) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-β—SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-β. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-β. Thus, our studies have unfolded the requirement of autophagy—TGF-β—SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Pokharel

Shil

Bose

2016

Front. Cell. Infect. Microbiol.

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“…Also, a deficiency in type I IFN production by cells from infants 47 and from neonatal mice 48, 49 has been shown. In contrast, some studies show a higher level of IFN-α in nasopharyngeal wash in more severely sick infants compared to controls 50 .…”

Section: Innate Immune Responses To Rsvmentioning

confidence: 99%

“…They are activated by PRR signalling and pro-inflammatory mediators in the lung to increase their antigen processing and presentation capability and migrate to regional lymph nodes where they convey viral antigens to naïve T and B cells 83 . It is interesting to note that there are fewer DCs in the lungs and lymph nodes of infants and they are also less functional after RSV infection compared to those from adult lungs 49, 84, 85 . Also, fewer and less functional plasmacytoid DCs are found in young children 47, 86 .…”

Section: Adaptive Immune Responses To Rsvmentioning

confidence: 99%

“…Also, fewer and less functional plasmacytoid DCs are found in young children 47, 86 . Flt3 ligand subcutaneous administration to neonatal mice mobilises more lung DCs and results in less lung inflammation after re-infection with RSV 49 . Altogether, these data suggest that a correct DC response is vital for a balanced immune response during RSV infection.…”

Section: Adaptive Immune Responses To Rsvmentioning

confidence: 99%

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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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La muqueuse pulmonaire en période périnatale : un monde à comprendre pour lutter contre la sensibilité du jeune à la bronchiolite

Chottin

Marquant

Saint‐Criq

et al. 2022

Revue des Maladies Respiratoires

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Flt3 ligand improves the innate response to respiratory syncytial virus and limits lung disease upon RSV reexposure in neonate mice

Cited by 28 publications

References 25 publications

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Respiratory syncytial virus infection: an innate perspective

La muqueuse pulmonaire en période périnatale : un monde à comprendre pour lutter contre la sensibilité du jeune à la bronchiolite

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