Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local Th2-like response

Kristjánsson, Sigurður; Bjarnarson, Stefania P.; Wennergren, Göran; Palsdottir, Aslaug H.; Arnadottir, Thorgerdur; Haraldsson, Ásgeir; Jónsdóttir, Ingileif

doi:10.1016/j.jaci.2005.07.012

Cited by 153 publications

(130 citation statements)

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“…The overall functional capacities of human infant T cells as being skewed toward Th2 or antiinflammatory responses (8) is largely derived from studies of umbilical cord blood (24)(25)(26). Measuring the in vivo infant immune response to VRTI has been more challenging, and has involved characterization of cells and cytokines in peripheral blood (6,21,27,28), nasopharyngeal washes (29,30), or tracheal aspirates (31,32). However, sampling remains limited, and unifying immune parameters related to disease outcome and severity has not emerged.…”

Section: Discussionmentioning

confidence: 99%

Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Connors

Ravindranath²,

Bickham

et al. 2016

Am J Respir Cell Mol Biol

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Infants and young children are disproportionately susceptible to severe complications from respiratory viruses, although the underlying mechanisms remain unknown. Recent studies show that the T cell response in the lung is important for protective responses to respiratory infections, although details on the infant/pediatric respiratory immune response remain sparse. The objectives of the present study were to characterize the local versus systemic immune response in infants and young children with respiratory failure from viral respiratory tract infections and its association to disease severity. Daily airway secretions were sampled from infants and children 4 years of age and younger receiving mechanical ventilation owing to respiratory failure from viral infection or noninfectious causes. Samples were examined for immune cell composition and markers of T cell activation. These parameters were then correlated with clinical disease severity. Innate immune cells and total CD31 T cells were present in similar proportions in airway aspirates derived from infected and uninfected groups; however, the CD8:CD4 T cell ratio was markedly increased in the airways of patients with viral infection compared with uninfected patients, and specifically in infected infants with acute lung injury. T cells in the airways were phenotypically and functionally distinct from those in blood with activated/memory phenotypes and increased cytotoxic capacity. We identified a significant increase in airway cytotoxic CD81 T cells in infants with lung injury from viral respiratory tract infection that was distinct from the T cell profile in circulation and associated with increasing disease severity. Airway sampling could therefore be diagnostically informative for assessing immune responses and lung damage.

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Section: Discussionmentioning

confidence: 99%

Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Connors

Ravindranath²,

Bickham

et al. 2016

Am J Respir Cell Mol Biol

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“…Infection with RSV during the first 3 months of life has been shown to induce a Th2-biased response compared to infection of older infants, based on an analysis of cytokines in respiratory secretions (88). Interestingly, this also was true of infants infected with HPIV or influenza virus and thus may be more related to host age rather than virus (88), but the overall impact of this effect is likely to be greater for RSV, since it infects patients with a greater frequency at this young age. Infection in a Th2-biased environment has the potential to affect the quality of the primary and recall responses.…”

Section: Rsv Is Not Highly Cytopathic or Invasivementioning

confidence: 99%

Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis

Collins¹,

Graham

2008

J Virol

423

478

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Human respiratory syncytial virus (RSV) was first isolated in 1956 from a laboratory chimpanzee with upper respiratory tract disease (for general reviews, see references 21, 57, 102, and 145). RSV was quickly determined to be of human origin and was shown to be the leading worldwide viral agent of serious pediatric respiratory tract disease. In a 13-year prospective study of infants and children in the United States, RSV was detected in 43%, 25%, 11%, and 10% of pediatric hospitalizations for bronchiolitis, pneumonia, bronchitis, and croup, respectively (110). Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by 2 years of age. The rate of hospitalization for primary infection is approximately 0.5% but can vary by situation and ethnic group and can be as high as 25% (77).RSV also is a significant cause of morbidity and mortality in the elderly, with an impact approaching that of nonpandemic influenza virus (39). RSV readily infects severely immunocompromised individuals, most notably allogeneic bone marrow transplant recipients, causing high mortality. RSV also makes a substantial contribution to upper respiratory tract disease in individuals of all ages (59,65 Although RSV has a single serotype, reinfection can occur throughout life. RSV in yearly winter/early spring epidemics in temperate regions; elsewhere, the timing of RSV activity can vary widely with the locale. The RSV reservoir in the offseason is unknown. Strains circulate quickly around the earth (150). Neither a vaccine nor an effective antiviral therapy is available, although there is active research in both areas (23,78,138). However, infants at high risk for serious disease can receive passive immunoprophylaxis during the epidemic season by a monthly injection of a commercial RSV-neutralizing monoclonal antibody, palivizumab (Synagis), which provides a 55% reduction in RSV-associated hospitalization (17). THE VIRUSRSV (family Paramyxoviridae, order Mononegavirales) is an enveloped virus with a single-stranded negative-sense RNA genome of 15.2 kb (21). There are animal versions of RSV, including bovine RSV (BRSV) and pneumonia virus of mice (PVM), suggesting that species jumping occurred during the evolution of these viruses. However, there is no animal reservoir for human RSV.Efficient infection by RSV of established cell lines in vitro involves binding to cell-surface glycosaminoglycans (62). However, it is not known how closely this binding models attachment in vivo or whether it is an initial interaction that is followed by a second, higher-affinity step that remains to be identified. The nucleocapsid gains entry to the cytoplasm by membrane fusion; surprisingly, this may involve clathrin-mediated endocytosis rather than surface fusion typical of paramyxoviruses (85). Viral gene expression and RNA replication occur in the cytoplasm, and virions acquire a lipid envelope by budding through the plasmid membrane (Fig. 1). Virions are pleomorphic and include spheres ...

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“…The reduced IFN-γ-dependent viral clearance may be related to reduced T-helper (Th)1 function, based on the observation that acute RSV bronchiolitis elicits an imbalance in Th1/Th2 cytokines present in airways secretions and produced by peripheral blood mononuclear cells (PBMCs), including a shift toward a Th2-type response [45]. Such preferential promotion of Th2-like responses in the airways with local production of interleukin (IL)-4, IL-5 and macrophage inflammatory protein-1β, and infiltration and activation of eosinophils, has been reported when RSV infection occurs during early infancy [46]. This decrease in IFN-γ production by PBMCs in infants with RSV bronchiolitis contributes to the severity of the disease since it is associated with a depressed lymphoproliferative response [47].…”

Section: Rsv Infection and Host Immune Responsementioning

confidence: 99%

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

2014

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There is evidence that respiratory viruses play a key role in the development and exacerbation of obstructive respiratory diseases in children. This review attempts to juxtapose the separate profiles and prototypes of pathogenenetic mechanisms represented by the two most common amongst such viruses: respiratory syncytial virus (RSV) and human rhinovirus (HRV).RSV represents the most common agent of severe airway disease in infants and young children, and is predominant in winter months. Large epidemiological studies have revealed an unequivocal relationship between RSV infection and subsequent wheezing into childhood, thought to be related to long-term changes in neuroimmune control of the airways rather than allergic sensitisation.HRV is a highly diverse group of viruses that affect subjects of all ages, is ubiquitous and occurs yearround. In contrast to RSV, infections with HRV cause minimal cytotoxicity but induce a rapid production of cytokines and chemokines with amplification of the inflammatory response. The susceptibility to HRVinduced bronchiolitis and subsequent wheezing appears to be linked to individual predisposition since it is often associated with a family or personal history of asthma/atopy.Thus, RSV probably serves as an "inducer" rather than a "trigger". Conversely, HRVs seem to serve as a "trigger" rather than an "inducer" in predisposed individuals. @ERSpublications Comprehensive overview of the different roles of RSV and HRV in the pathogenesis of recurrent wheezing in childhood

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Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local Th2-like response

Cited by 153 publications

References 38 publications

Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

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Respiratory syncytial virus and other respiratory viruses during the first 3 months of life promote a local Th2-like response

Cited by 153 publications

References 38 publications

Airway CD8+T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Airway CD8+T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis

Infantile respiratory syncytial virus and human rhinovirus infections: respective role in inception and persistence of wheezing

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Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection

Airway CD8⁺T Cells Are Associated with Lung Injury during Infant Viral Respiratory Tract Infection