scholarly journals IFN-γ Attenuates Eosinophilic Inflammation but Is Not Essential for Protection against RSV-Enhanced Asthmatic Comorbidity in Adult Mice

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 147
Author(s):  
Abenaya Muralidharan ◽  
Md Bashir Uddin ◽  
Christopher Bauer ◽  
Wenzhe Wu ◽  
Xiaoyong Bao ◽  
...  
Keyword(s):  
Critical Role ◽  
Lung Damage ◽  
Eosinophil Infiltration ◽  
Severe Illness ◽  
Eosinophilic Inflammation ◽  
Adult Mice ◽  
Helper Cell Type ◽  
Rsv Infection ◽  
Ifn Γ ◽  
Syncytial Virus

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage but has no significant effect on OVA-induced eosinophilia. Compared with WT controls, RSV infection of asthmatic Ifng−/− mice results in increased airway eosinophil accumulation. However, a comparable increase in eosinophilia was detected in house dust mite (HDM)-induced asthmatic Ifng−/− mice in the absence of RSV infection. Furthermore, neither WT nor Ifng−/− mice exhibit apparent eosinophil infiltration during RSV infection alone. Together, these findings indicate that, despite its critical role in limiting eosinophilic inflammation during asthma, IFN-γ is not essential for protection against RSV-induced exacerbation of asthmatic inflammation in adult mice.

scholarly journals Fcγ Receptor IIa (FCGR2A) Polymorphism Is Associated With Severe Respiratory Syncytial Virus Disease in Argentinian Infants

2020 ◽  
Vol 10 ◽  
Author(s):  
María Pía Holgado ◽  
Silvina Raiden ◽  
Inés Sananez ◽  
Vanesa Seery ◽  
Leonardo De Lillo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Disease ◽  
Severe Disease ◽  
Critical Role ◽  
Fcγ Receptor ◽  
Factors Associated ◽  
Severe Group ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Relationship

BackgroundMost patients with respiratory syncytial virus (RSV) infection requiring hospitalization have no risk factors for severe disease. Genetic variation in the receptor for the Fc portion of IgG (FcγR) determines their affinity for IgG subclasses driving innate and adaptive antiviral immunity. We investigated the relationship between FcγRIIa-H131R polymorphism and RSV disease.MethodsBlood samples were collected from 182 infants ≤24-month-old (50 uninfected, 114 RSV-infected with moderate course and 18 suffering severe disease). FcγRIIa-H131R SNP genotypic frequencies (HH, HR, RR) and anti-RSV IgG1, IgG2 and IgG3 levels were studied.ResultsGenotypic frequencies for FcγRIIa-H131R SNP were comparable between uninfected and RSV-infected infants. In contrast, we found a significant higher frequency of HH genotype in severe RSV-infected children compared to moderate patients. Among severe group, HH infants presented more factors associated to severity than HR or RR patients did. Furthermore, compared to moderate RSV-infected infants, severe patients showed higher levels of anti-RSV IgG1 and IgG3.ConclusionsWe found an association between an FcγRIIa (H131) polymorphism and severe RSV disease, which points towards a critical role for interactions between FcγRs and immune complexes in RSV pathogenesis. This genetic factor could also predict the worse outcome and identify those infants at risk during hospitalization.

scholarly journals The Human Immune Response to Respiratory Syncytial Virus Infection

2017 ◽  
Vol 30 (2) ◽  
pp. 481-502 ◽  
Author(s):  
Clark D. Russell ◽  
Stefan A. Unger ◽  
Marc Walton ◽  
Jürgen Schwarze
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
T Cell ◽  
T Cell Response ◽  
Rsv Infection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
Human Immune ◽  
Syncytial Virus

SUMMARY Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and in vitro studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8+ T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8+ T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.

scholarly journals CD25+ Natural Regulatory T Cells Are Critical in Limiting Innate and Adaptive Immunity and Resolving Disease following Respiratory Syncytial Virus Infection

2010 ◽  
Vol 84 (17) ◽  
pp. 8790-8798 ◽  
Author(s):  
Debbie C. P. Lee ◽  
James A. E. Harker ◽  
John S. Tregoning ◽  
Sowsan F. Atabani ◽  
Cecilia Johansson ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Viral Infections ◽  
Lavage Fluid ◽  
Rsv Infection ◽  
Ifn Γ ◽  
Syncytial Virus

ABSTRACT Regulatory CD4+ T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4+ Foxp3+ CD25+ natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25+ natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL-6) and gamma interferon (IFN-γ). CD25+ natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-γ and tumor necrosis factor alpha (TNF-α) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections.

Osteopontin (OPN) Plays a Critical Role in Respiratory Syncytial Virus (RSV) Infection

2015 ◽  
Vol 135 (2) ◽  
pp. AB109
Author(s):  
Viviana P. Sampayo-Escobar ◽  
Terianne M. Wong ◽  
Sandhya Boyapalle ◽  
Raminder Bedi ◽  
Subhra Mohapatra ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Critical Role ◽  
Rsv Infection ◽  
Syncytial Virus

scholarly journals Interferon γ Stabilizes the T Helper Cell Type 1 Phenotype

2001 ◽  
Vol 194 (2) ◽  
pp. 165-172 ◽  
Author(s):  
Yongkang Zhang ◽  
Ron Apilado ◽  
John Coleman ◽  
Shlomo Ben-Sasson ◽  
Sharon Tsang ◽  
...  
Keyword(s):  
Critical Role ◽  
Interferon Γ ◽  
T Helper Cell ◽  
Helper Cell ◽  
Wild Type ◽  
T Helper ◽  
Helper Cell Type ◽  
Ifn Γ ◽  
Th 1

T helper cell (Th)1-primed CD4 T cells from wild-type donors make little interleukin (IL)-4 when restimulated under Th2 conditions. However, such restimulation of Th1-primed cells from interferon (IFN)-γ2/− or IFN-γ receptor (IFN-γR)−/− mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-γ to the priming culture markedly diminished the capacity of Th1-primed IFN-γ2/− cells to express IL-4. Even IFN-γ–producing cells from IFN-γR−/− mice could acquire IL-4–producing capacity. Thus, IFN-γ is not required for the development of IFN-γ–producing capacity, but it plays a critical role in suppressing the IL-4–producing potential of Th1 cells.

scholarly journals Airway gene expression correlates of RSV disease severity and microbiome composition in infants

2020 ◽  
Author(s):  
Chin-Yi Chu ◽  
Xing Qiu ◽  
Matthew N McCall ◽  
Lu Wang ◽  
Anthony Corbett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Disease Severity ◽  
Clinical Symptoms ◽  
Expression Patterns ◽  
Gene Expression Signature ◽  
Illness Severity ◽  
Severe Illness ◽  
Gene Expression Patterns ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract Rationale Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants. The causes and correlates of severe illness in the majority of infants are poorly defined. Objectives We identified molecular correlates of illness severity from the airways of infants infected with RSV. Methods We recruited a cohort of RSV-infected infants and simultaneously assayed the molecular status of their airways and the presence of airway microbiota. Rigorous statistical approaches identified gene expression patterns associated with disease severity and microbiota composition, separately and in combination. Measurements and Main Results We measured comprehensive airway gene expression patterns in 106 infants with primary RSV infection. We identified an airway gene expression signature of severe illness dominated by excessive chemokine expression. We also found an association between H. influenzae, disease severity and airway lymphocyte accumulation. Exploring the time of onset of clinical symptoms revealed acute activation of interferon (IFN) signaling following RSV infection in infants with mild or moderate illness, which was absent in subjects with severe illness. Conclusion Our data reveal that airway gene expression patterns distinguish mild/moderate from severe illness severity. Furthermore, our data identify biomarkers that may be therapeutic targets or useful for measuring efficacy of intervention responses.

Maternal gut microbiome regulates immunity to RSV infection in offspring

2021 ◽  
Vol 218 (11) ◽  
Author(s):  
Wendy Fonseca ◽  
Carrie-Anne Malinczak ◽  
Kei Fujimura ◽  
Danny Li ◽  
Kathryn McCauley ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Maternal Plasma ◽  
Metabolic Reprogramming ◽  
Mucus Production ◽  
Intrinsic Factors ◽  
Adult Mice ◽  
Immune Alterations ◽  
Rsv Infection ◽  
Maternal Supplementation ◽  
Syncytial Virus

Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell–mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.

Differences in respiratory syncytial virus and influenza infection in a house-dust-mite-induced asthma mouse model: consequences for steroid sensitivity

2013 ◽  
Vol 125 (12) ◽  
pp. 565-574 ◽  
Author(s):  
Hiroki Mori ◽  
Nicole S. Parker ◽  
Deborah Rodrigues ◽  
Kathryn Hulland ◽  
Deborah Chappell ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Mouse Model ◽  
Influenza Infection ◽  
Prednisolone Treatment ◽  
Dust Mite ◽  
Rsv Infection ◽  
Ifn Γ ◽  
Syncytial Virus ◽  
Clinical Asthma

A significant number of clinical asthma exacerbations are triggered by viral infection. We aimed to characterize the effect of virus infection in an HDM (house dust mite) mouse model of asthma and assess the effect of oral corticosteroids. HDM alone significantly increased eosinophils, lymphocytes, neutrophils, macrophages and a number of cytokines in BAL (bronchoalveolar lavage), all of which were sensitive to treatment with prednisolone (with the exception of neutrophils). Virus infection also induced cell infiltration and cytokines. RSV (respiratory syncytial virus) infection in HDM-treated animals further increased all cell types in BAL (except eosinophils, which declined), but induced no further increase in HDM-elicited cytokines. However, while HDM-elicited TNF-α (tumour necrosis factor-α), IFN-γ (interferon-γ), IL (interleukin)-2, IL-5 and IL-10 were sensitive to prednisolone treatment, concomitant infection with RSV blocked the sensitivity towards steroid. In contrast, influenza infection in HDM- challenged animals resulted in increased BAL lymphocytes, neutrophils, IFN-γ, IL-1β, IL-4, IL-5, IL-10 and IL-12, but all were attenuated by prednisolone treatment. HDM also increased eNO (exhaled NO), which was further increased by concomitant virus infection. This increase was only partially attenuated by prednisolone. RSV infection alone increased BAL mucin. However, BAL mucin was increased in HDM animals with virus infection. Chronic HDM challenge in mice elicits a broad inflammatory response that shares many characteristics with clinical asthma. Concomitant influenza or RSV infection elicits differing inflammatory profiles that differ in their sensitivity towards steroids. This model may be suitable for the assessment of novel pharmacological interventions for asthmatic exacerbation.

scholarly journals Respiratory Syncytial Virus-Mediated NF-κB p65 Phosphorylation at Serine 536 Is Dependent on RIG-I, TRAF6, and IKKβ

2010 ◽  
Vol 84 (14) ◽  
pp. 7267-7277 ◽  
Author(s):  
Fabrice Yoboua ◽  
Alexis Martel ◽  
Annick Duval ◽  
Espérance Mukawera ◽  
Nathalie Grandvaux
Keyword(s):  
Respiratory Syncytial Virus ◽  
Critical Role ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Proinflammatory Response ◽  
Cytokines And Chemokines ◽  
Upstream Regulator ◽  
Rsv Infection ◽  
Oxidase Enzyme ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is the etiological agent of acute respiratory diseases, such as bronchiolitis and pneumonia. The exacerbated production of proinflammatory cytokines and chemokines in the airways in response to RSV is an important pillar in the development of these pathologies. As such, a keen understanding of the mechanisms that modulate the inflammatory response during RSV infection is of pivotal importance to developing effective treatment. The NF-κB transcription factor is a major regulator of proinflammatory cytokine and chemokine genes. However, RSV-mediated activation of NF-κB is far from characterized. We recently demonstrated that aside from the well-characterized IκBα phosphorylation and degradation, the phosphorylation of p65 at Ser536 is an essential event regulating the RSV-mediated NF-κB-dependent promoter transactivation. In the present study, using small interfering RNA and pharmacological inhibitors, we now demonstrate that RSV sensing by the RIG-I cytoplasmic receptor triggers a signaling cascade involving the MAVS and TRAF6 adaptors that ultimately leads to p65ser536 phosphorylation by the IKKβ kinase. In a previous study, we highlighted a critical role of the NOX2-containing NADPH oxidase enzyme as an upstream regulator of both the IκBαSer32 and p65Ser536 in human airway epithelial cells. Here, we demonstrate that inhibition of NOX2 significantly decreases IKKβ activation. Taken together, our data identify a new RIG-I/MAVS/TRAF6/IKKβ/p65Ser536 pathway placed under the control of NOX2, thus characterizing a novel regulatory pathway involved in NF-κB-driven proinflammatory response in the context of RSV infection.

Sign in / Sign up

Export Citation Format

Share Document