T cell responses are elicited against Respiratory Syncytial Virus in the absence of signalling through TLRs, RLRs and IL-1R/IL-18R

Goritzka, Michelle; Pereira, Catherine; Makris, Spyridon; Durant, Lydia; Johansson, Cecilia

doi:10.1038/srep18533

Cited by 23 publications

(23 citation statements)

References 47 publications

(66 reference statements)

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“…Second, a MAVS independent mechanism could drive the maturation and antigen presentation capacity of DCs. We have previously shown that mice deficient in MyD88/TRIF and MAVS can mount T cell responses albeit to a reduced level compared to wt mice ( 32 ). In addition, Bhoj et al .…”

Section: Discussionmentioning

confidence: 99%

MAVS Deficiency Is Associated With a Reduced T Cell Response Upon Secondary RSV Infection in Mice

et al. 2020

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Infections with respiratory syncytial virus (RSV) occurs repeatedly throughout life because sustained, protective memory responses fail to develop. Why this occurs is not known. During RSV infection the recognition of the virus via the cytosolic RIG-I like receptors and signaling via the adaptor protein MAVS is crucial for mounting an innate immune response. However, if this signaling pathway is important for T cell responses during primary infection and during re-infection is not fully elucidated. We describe a second peak of pro-inflammatory mediators during the primary immune response to RSV that coincides with the arrival of T cells into the lung. This second peak of cytokines/chemokines is regulated differently than the early peak and is largely independent of signaling via MAVS. This was concurrent with Mavs −/− mice mounting a strong T cell response to primary RSV infection, with robust IFN-γ; and Granzyme B production. However, after RSV re-infection, Mavs −/− mice showed fewer CD4 + and CD8 + short term memory T cells and their capacity to produce IFN-γ; and Granzyme B, was decreased. In sum, cytosolic recognition of RSV is important not only for initiating innate anti-viral responses but also for generating or maintaining efficient, short term T cell memory responses.

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Section: Discussionmentioning

confidence: 99%

MAVS Deficiency Is Associated With a Reduced T Cell Response Upon Secondary RSV Infection in Mice

et al. 2020

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“…Partial deletion of the amino-terminal RNA-binding domain of NS1 from influenza A rescues the production of IL-1β and IL-18 during infection, suggesting that this domain antagonizes the activation of caspase 1 ( 167 ). Intriguingly, Goritzka et al recently showed that while early lung infiltration of immune cells and levels of proinflammatory mediators were abrogated in Myd88 / Trif / Mavs −/− mice (which lack TLR, RLR, and IL-1R signaling), there was no subsequent effect upon the induction of RSV-specific CD8 + T cells ( 168 ). This implies that caspase-1 and TLR7 are essential to the development of adaptive immune responses to influenza virus, while the RIG-I pathway is more important in RSV but that redundant downstream pathways exist to induce cell-mediated immunity even in its absence.…”

Section: Innate Immunity Following Respiratory Virus Infectionmentioning

confidence: 99%

Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

2018

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Respiratory syncytial virus (RSV) and influenza are among the most important causes of severe respiratory disease worldwide. Despite the clinical need, barriers to developing reliably effective vaccines against these viruses have remained firmly in place for decades. Overcoming these hurdles requires better understanding of human immunity and the strategies by which these pathogens evade it. Although superficially similar, the virology and host response to RSV and influenza are strikingly distinct. Influenza induces robust strain-specific immunity following natural infection, although protection by current vaccines is short-lived. In contrast, even strain-specific protection is incomplete after RSV and there are currently no licensed RSV vaccines. Although animal models have been critical for developing a fundamental understanding of antiviral immunity, extrapolating to human disease has been problematic. It is only with recent translational advances (such as controlled human infection models and high-dimensional technologies) that the mechanisms responsible for differences in protection against RSV compared to influenza have begun to be elucidated in the human context. Influenza infection elicits high-affinity IgA in the respiratory tract and virus-specific IgG, which correlates with protection. Long-lived influenza-specific T cells have also been shown to ameliorate disease. This robust immunity promotes rapid emergence of antigenic variants leading to immune escape. RSV differs markedly, as reinfection with similar strains occurs despite natural infection inducing high levels of antibody against conserved antigens. The immunomodulatory mechanisms of RSV are thus highly effective in inhibiting long-term protection, with disturbance of type I interferon signaling, antigen presentation and chemokine-induced inflammation possibly all contributing. These lead to widespread effects on adaptive immunity with impaired B cell memory and reduced T cell generation and functionality. Here, we discuss the differences in clinical outcome and immune response following influenza and RSV. Specifically, we focus on differences in their recognition by innate immunity; the strategies used by each virus to evade these early immune responses; and effects across the innate-adaptive interface that may prevent long-lived memory generation. Thus, by comparing these globally important pathogens, we highlight mechanisms by which optimal antiviral immunity may be better induced and discuss the potential for these insights to inform novel vaccines.

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“…This indicates that the interplay between genetics and the environment, including the microbiota and co-infections, will be part of the severity of disease caused by RSV ( Figure 1). Interestingly, even mice genetically lacking the ability to signal via all TLRs and RLRs are able to control RSV infection and mount T cell responses to the virus 63 . This suggests that additional mechanisms for detecting RSV infection exist that can compensate for the lack of PRR signalling.…”

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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T cell responses are elicited against Respiratory Syncytial Virus in the absence of signalling through TLRs, RLRs and IL-1R/IL-18R

Cited by 23 publications

References 47 publications

MAVS Deficiency Is Associated With a Reduced T Cell Response Upon Secondary RSV Infection in Mice

MAVS Deficiency Is Associated With a Reduced T Cell Response Upon Secondary RSV Infection in Mice

Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus

Respiratory syncytial virus infection: an innate perspective

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