Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis

McNamara, Paul; Flanagan, Brian; Baldwin, L.; Newland, Paul; Smyth, Rosalind L

doi:10.1016/s0140-6736(04)15838-8

Cited by 95 publications

(82 citation statements)

References 26 publications

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“…IL-9 is present in the respiratory secretions of infants with RSV bronchiolitis (13). Children suffering from RSV bronchiolitis tend to produce stronger Th2 (i.e., increased IL-4) and weaker Th1 (i.e., reduced IFN-␥) responses to viral infection than children who exhibit mild disease (18).…”

Section: Discussionmentioning

confidence: 99%

“…Children suffering from RSV bronchiolitis tend to produce stronger Th2 (i.e., increased IL-4) and weaker Th1 (i.e., reduced IFN-␥) responses to viral infection than children who exhibit mild disease (18). McNamara et al have previously highlighted the potential importance of IL-9 in promoting this detrimental response (13). Our finding that IL-9 depletion during the primary response to the RSV G protein (the only protein expressed by the virus known to promote Th2 responses) decreases both IFN-␥ and IL-4 secretion by G-specific T cells, as well as IL-4 and IL-5 secretion by memory T cells, and alleviates Th2-mediated phenomena (e.g., eosinophil influx) upon viral challenge further supports the concept that early IL-9 production is critical for setting the pattern of T cell cytokine secretion.…”

Section: Discussionmentioning

confidence: 99%

“…IL-9 is made by CD4 T cells, primarily those of the Th2 subset (12,13), but is also produced by eosinophils, mast cells, and neutrophils (14,15). It acts as a T cell growth factor, enhances IL-4-mediated IgE production by B cells, promotes the survival and activation of eosinophils and mast cells, increases expression of IgER␣, and thereby affects IgE-mediated immunity (12).…”

Section: Il-9 Regulates Pathology During Primary and Memorymentioning

confidence: 99%

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IL-9 Regulates Pathology during Primary and Memory Responses to Respiratory Syncytial Virus Infection

Dodd

Lum

Goulding

et al. 2009

The Journal of Immunology

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IL-9 is a cytokine of great current interest associated with allergic/Th2 responses. High levels of IL-9 are present in bronchial secretions from infants with respiratory syncytial virus (RSV) bronchiolitis. To test its effects in RSV disease with a Th2 profile, BALB/c mice were vaccinated with recombinant vaccinia virus expressing the RSV G protein. On RSV challenge, immunized mice developed augmented disease characterized by enhanced pulmonary Th2 and local IL-9 production peaking on days 7–10 of RSV infection. Depletion with anti-IL-9 Ab at vaccination or RSV challenge enhanced viral clearance. Depletion only at challenge had no effect on disease severity, whereas depletion at immunization and challenge enhanced Th1 responses, inhibited virus-specific IgG1 production, and enhanced disease severity. By contrast, depletion of IL-9 at immunization boosted IgG2a and inhibited the Th2 response and disease during subsequent infection without a concomitant increase in type 1 cytokines. Adoptive transfer of secondary memory CD4 T cells from the spleens of IL-9-depleted mice into naive recipients replicated many of the effects of depletion, indicating that IL-9 acts via CD4 T cells. Therefore, IL-9 is a previously unknown but key modulator of antiviral immunity, regulating T and B cell responses and having potent and specific effects on viral lung disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Il-9 Regulates Pathology During Primary and Memorymentioning

confidence: 99%

See 1 more Smart Citation

IL-9 Regulates Pathology during Primary and Memory Responses to Respiratory Syncytial Virus Infection

Dodd

Lum

Goulding

et al. 2009

The Journal of Immunology

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“…The mechanism by which RSV causes recurrent wheezing is not entirely clear. An influx of neutrophils to the airways prompted by the RSV infection may plausibly be associated with damage to the airway architecture, resulting in wheezing and shortness of breath when any subsequent viral infection occurs [125,126].…”

Section: Viral Respiratory Infectionsmentioning

confidence: 99%

Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing

et al. 2014

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Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease often originate early in life. In addition to a genetic predisposition, prenatal and early-life environmental exposures have a persistent impact on respiratory health. Acting during a critical phase of lung development, these factors may change lung structure and metabolism, and may induce maladaptive responses to harmful agents, which will affect the whole lifespan.Some environmental factors, such as exposure to cigarette smoke, type of childbirth and diet, may be modifiable, but it is more difficult to influence other factors, such as preterm birth and early exposure to viruses or allergens.Here, we bring together recent literature to analyse the critical aspects involved in the early stages of lung development, going back to prenatal and perinatal events, and we discuss the mechanisms by which noxious factors encountered early on may have a lifelong impact on respiratory health.We briefly comment on the need for early disease biomarkers and on the possible role of ''-omic'' technologies in identifying risk profiles predictive of chronic respiratory conditions. Such profiles could guide the ideation of effective preventive strategies and/or targeted early lifestyle or therapeutic interventions. @ERSpublications Early-life factors have a role in onset of asthma and COPD; early postnatal interventions may promote lung health http://ow.ly/BvUrx

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“…Less clear is the intriguing epidemiological link between infants who have severe RSV infections and develop asthma in subsequent years (10,(12)(13)(14). The primary immune response to RSV is characterized by a generalized inflammatory response (15)(16)(17)(18)(19)(20)(21)(22)(23). Depending on the time and conditions of infection, both Th1 and Th2 chemokines (small secreted peptides that regulate leukocyte trafficking) can be induced by RSV (18,24,25).…”

Section: R Espiratory Syncytial Virus (Rsv)mentioning

confidence: 99%

Respiratory Syncytial Virus Synergizes with Th2 Cytokines to Induce Optimal Levels of TARC/CCL17

Monick

Powers

Hassan

et al. 2007

The Journal of Immunology

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Respiratory syncytial virus (RSV) is a ubiquitous virus that preferentially infects airway epithelial cells, causing asthma exacerbations and severe disease in immunocompromised hosts. Acute RSV infection induces inflammation in the lung. Thymus- and activation-regulated chemokine (TARC) recruits Th2 cells to sites of inflammation. We found that acute RSV infection of BALB/c mice increased TARC production in the lung. Immunization of BALB/c mice with individual RSV proteins can lead to the development of Th1- or Th2-biased T cell responses in the lung after RSV infection. We primed animals with a recombinant vaccinia virus expressing either the RSV fusion (F) protein or the RSV attachment (G) protein, inducing Th1- and Th2-biased pulmonary memory T cell responses, respectively. After RSV infection, TARC production significantly increased in the vaccinia virus G-primed animals only. These data suggest a positive feedback loop for TARC production between RSV infection and Th2 cytokines. RSV-infected lung epithelial cells cultured with IL-4 or IL-13 demonstrated a marked increase in the production of TARC. The synergistic effect of RSV and IL-4/IL-13 on TARC production reflected differential induction of NFκB and STAT6 by the two stimuli (both are in the TARC promoter). These findings demonstrate that RSV induces a chemokine TARC that has the potential to recruit Th2 cells to the lung.

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Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis

Cited by 95 publications

References 26 publications

IL-9 Regulates Pathology during Primary and Memory Responses to Respiratory Syncytial Virus Infection

IL-9 Regulates Pathology during Primary and Memory Responses to Respiratory Syncytial Virus Infection

Early-life origins of chronic respiratory diseases: understanding and promoting healthy ageing

Respiratory Syncytial Virus Synergizes with Th2 Cytokines to Induce Optimal Levels of TARC/CCL17

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