scholarly journals Regulatory B Lymphocytes Colonize the Respiratory Tract of Neonatal Mice and Modulate Immune Responses of Alveolar Macrophages to RSV Infection in IL-10-Dependant Manner

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 822
Author(s):  
Daphné Laubreton ◽  
Carole Drajac ◽  
Jean-François Eléouët ◽  
Marie-Anne Rameix-Welti ◽  
Richard Lo-Man ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
B Lymphocytes ◽  
Alveolar Macrophages ◽  
Type I Interferons ◽  
Type I ◽  
Neonatal Lung ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with bronchiolitis severity. So far, little is known about how nBreg may contribute to neonatal immunopathology to RSV. We tracked nBreg in neonatal BALB/c mice and we investigated their impact on lung innate immunity, especially their crosstalk with alveolar macrophages (AMs) upon RSV infection. We showed that the colonization by nBreg during the first week of life is a hallmark of neonatal lung whereas this population is almost absent in adult lung. This particular period of age when nBreg are abundant corresponds to the same period when RSV replication in lungs fails to generate a type-I interferons (IFN-I) response and is not contained. When neonatal AMs are exposed to RSV in vitro, they produce IFN-I that in turn enhances IL-10 production by nBreg. IL-10 reciprocally can decrease IFN-I secretion by AMs. Thus, our work identified nBreg as an important component of neonatal lungs and pointed out new immunoregulatory interactions with AMs in the context of RSV infection.

scholarly journals Alveolar Macrophages Can Control Respiratory Syncytial Virus Infection in the Absence of Type I Interferons

2016 ◽  
Vol 8 (5) ◽  
pp. 452-463 ◽  
Author(s):  
Spyridon Makris ◽  
Monika Bajorek ◽  
Fiona J. Culley ◽  
Michelle Goritzka ◽  
Cecilia Johansson
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Replication ◽  
Alveolar Macrophages ◽  
Ex Vivo ◽  
Type I Interferons ◽  
Type I ◽  
Proinflammatory Mediators ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections. Immunity to RSV is initiated upon detection of the virus by pattern recognition receptors, such as RIG-I-like receptors. RIG-I-like receptors signal via MAVS to induce the synthesis of proinflammatory mediators, including type I interferons (IFNs), which trigger and shape antiviral responses and protect cells from infection. Alveolar macrophages (AMs) are amongst the first cells to encounter invading viruses and the ones producing type I IFNs. However, it is unclear whether IFNs act to prevent AMs from serving as vehicles for viral replication. In this study, primary AMs from MAVS (Mavs-/-)- or type I IFN receptor (Ifnar1-/-)-deficient mice were exposed to RSV ex vivo. Wild-type (wt) AMs but not Mavs-/- and Ifnar1-/- AMs produced inflammatory mediators in response to RSV. Furthermore, Mavs-/- and Ifnar1-/- AMs accumulated more RSV proteins than wt AMs, but the infection was abortive. Thus, RIG-I-like receptor-MAVS and IFNAR signalling are important for the induction of proinflammatory mediators from AMs upon RSV infection, but this signalling is not central for controlling viral replication. The ability to restrict viral replication makes AMs ideal sensors of RSV infection and important initiators of immune responses in the lung.

scholarly journals Control of IFN-I responses by the aminopeptidase IRAP in neonatal C57BL/6 alveolar macrophages during RSV infection

2021 ◽  
Author(s):  
Carole Drajac ◽  
Daphné Laubreton ◽  
Quentin Marquant ◽  
Claire Chottin ◽  
Cécile Ferret ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Wild Type ◽  
Antiviral Responses ◽  
Age Dependent ◽  
Rsv Infection ◽  
Syncytial Virus

AbstractRespiratory Syncytial Virus (RSV) is the major cause of lower respiratory tract infection in infants, in whom, the sensing of RSV by innate immune receptors and its regulation are still poorly described. However, the severe bronchiolitis following RSV infection in neonates has been associated with a defect in type I interferons (IFN-I) production, a cytokine produced mainly by alveolar macrophages (AMs) upon RSV infection in adults. In the present study, neonatal C57BL/6 AMs mobilized very weakly the IFN-I pathway upon RSV infection in vitro and failed to restrain virus replication. However, IFN-I productions by neonatal AMs were substantially increased by the deletion of Insulin-Responsive AminoPeptidase (IRAP), a protein previously involved in the regulation of IFN-I production by dendritic cells. Moreover, neonatal IRAPKO AMs showed a higher expression of IFN-stimulated genes than their wild-type C57BL/6 counterpart. Interestingly, depletion of IRAP did not affect adult AM responses. Finally, we demonstrated that newborn IRAPKO mice infected with RSV had more IFN-I in their lungs and eliminated the virus more efficiently than WT neonates. Taken together, early-life susceptibility to RSV infection may be related to an original age-dependent suppressive function of IRAP on the IFN-I driven-antiviral responses in neonatal AMs.

scholarly journals Differential Role of Anti-Viral Sensing Pathway for the Production of Type I Interferon β in Dendritic Cells and Macrophages Against Respiratory Syncytial Virus A2 Strain Infection

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 62 ◽  
Author(s):  
Dong Oh ◽  
Tae Kim ◽  
Heung Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Primary Response ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifns ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Mitochondrial Antiviral Signaling

Respiratory syncytial virus (RSV) is a major cause of respiratory infectious disease in infants and young children. Dendritic cells (DCs) and macrophages (MACs) are known to play important roles in RSV recognition, and in the production of type I interferons (IFNs) and pro-inflammatory cytokine in RSV infection. Toll-like receptor 7 (TLR7), myeloid differentiation primary response 88 (MyD88), and mitochondrial antiviral-signaling protein (MAVS) are known to be important for the RSV sensing pathway in DCs and MACs. However, despite the critical roles of type I IFNs in the anti-RSV immune response, the pattern recognition receptors (PRRs) that are required for RSV sensing in DCs and MACs remain unclear. Here, we investigate the pathway activated by RSV A2 strain infection using an IFN-β/YFP reporter mouse model to visualize IFN-β-producing cells and in vitro RSV infection in bone marrow-derived DCs (BM-DCs) and macrophages (BM-DMs). We present our finding that MyD88, but not TLR7, are important for RSV recognition and type I IFN and pro-inflammatory production in DCs and MACs. MAVS-deficient BM-DCs and BM-DMs show impaired induction of IFN-β production upon RSV stimulation, and this effect is RSV replication-dependent. Our study provides information on cell type-specific PRR requirements in innate immune responses against RSV infection.

Reappraisal of respiratory syncytial virus as an aetiology of severe acute lower respiratory tract infections in children younger than 5 years in Nigeria

2019 ◽  
Vol 113 (8) ◽  
pp. 446-452
Author(s):  
Damilola M Oladele ◽  
Dimeji P Oladele ◽  
Rasheedat M Ibraheem ◽  
Mohammed B Abdulkadir ◽  
Rasaki Adewole Raheem ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Preventive Strategy ◽  
Lower Respiratory Tract Infections ◽  
Cross Sectional ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. Methods We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2–59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. Results The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. Conclusions RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

scholarly journals Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

2014 ◽  
Vol 45 (3) ◽  
pp. 718-725 ◽  
Author(s):  
Corné H. van den Kieboom ◽  
Inge M.L. Ahout ◽  
Aldert Zomer ◽  
Kim H. Brand ◽  
Ronald de Groot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Pathogen Detection ◽  
Severe Disease ◽  
Host Gene ◽  
Host Gene Expression ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection.To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7.These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients.Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections.

scholarly journals RSV attenuates epithelial cell restitution by inhibiting actin cytoskeleton-dependent cell migration

2021 ◽  
Author(s):  
Debra T Linfield ◽  
Nannan Gao ◽  
Andjela Raduka ◽  
Terri J Harford ◽  
Giovanni Piedimonte ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Wound Repair ◽  
Focal Adhesions ◽  
Fiber Formation ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

The airway epithelium's ability to repair itself after injury, known as epithelial restitution, is an essential mechanism enabling the respiratory tract's normal functions. Respiratory Syncytial Virus (RSV) is the leading cause of lower respiratory tract infections worldwide. We sought to determine whether RSV delays the airway epithelium wound repair process both in vitro and in vivo. We found that RSV infection attenuated epithelial cell migration, a step in wound repair, promoted stress fiber formation, and mediated assembly of large focal adhesions (FA). Inhibition of Rho kinase (ROCK), a master regulator of actin function, reversed these effects. There was increased RhoA and phospho-myosin light chain (pMLC2) following RSV infection. In vivo, mice were intraperitoneally inoculated with naphthalene to induce lung injury, followed by RSV infection. RSV infection delayed re-epithelialization. There were increased concentrations of pMLC2 in day 7 naphthalene plus RSV animals which normalized by day 14. This study suggests a key mechanism by which RSV infection delays wound healing.

scholarly journals Long Noncoding RNA NRAV Promotes Respiratory Syncytial Virus Replication by Targeting the MicroRNA miR-509-3p/Rab5c Axis To Regulate Vesicle Transportation

2020 ◽  
Vol 94 (10) ◽  
Author(s):  
Jian Li ◽  
Miao Li ◽  
Xiuli Wang ◽  
Mengfei Sun ◽  
Cuiqing Ma ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Respiratory Virus ◽  
Antiviral Response ◽  
Negative Regulator ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

ABSTRACT Respiratory syncytial virus (RSV) is an enveloped RNA virus which is responsible for approximately 80% of lower respiratory tract infections in children. Current lines of evidence have supported the functional involvement of long noncoding RNA (lncRNA) in many viral infectious diseases. However, the overall biological effect and clinical role of lncRNAs in RSV infection remain unclear. In this study, lncRNAs related to respiratory virus infection were obtained from the lncRNA database, and we collected 144 clinical sputum specimens to identify lncRNAs related to RSV infection. Quantitative PCR (qPCR) detection indicated that the expression of lncRNA negative regulator of antiviral response (NRAV) in RSV-positive patients was significantly lower than that in uninfected patients, but lncRNA psoriasis-associated non-protein coding RNA induced by stress (PRINS), nuclear paraspeckle assembly transcript 1 (NEAT1), and Nettoie Salmonella pas Theiler’s (NeST) showed no difference in vivo and in vitro. Meanwhile, overexpression of NRAV promoted RSV proliferation in A549 and BEAS-2B cells, and vice versa, indicating that the downregulation of NRAV was part of the host antiviral defense. RNA fluorescent in situ hybridization (FISH) confirmed that NRAV was mainly located in the cytoplasm. Through RNA sequencing, we found that Rab5c, which is a vesicle transporting protein, showed the same change trend as NRAV. Subsequent investigation revealed that NRAV was able to favor RSV production indirectly by sponging microRNA miR-509-3p so as to release Rab5c and facilitate vesicle transportation. The study provides a new insight into virus-host interaction through noncoding RNA, which may contribute to exploring potential antivirus targets for respiratory virus. IMPORTANCE The mechanism of interaction between RSV and host noncoding RNAs is not fully understood. In this study, we found that the expression of long noncoding RNA (lncRNA) negative regulator of antiviral response (NRAV) was reduced in RSV-infected patients, and overexpression of NRAV facilitated RSV production in vitro, suggesting that the reduction of NRAV in RSV infection was part of the host antiviral response. We also found that NRAV competed with vesicle protein Rab5c for microRNA miR509-3p in cytoplasm to promote RSV vesicle transport and accelerate RSV proliferation, thereby improving our understanding of the pathogenic mechanism of RSV infection.

scholarly journals 738. Role of Respiratory Syncytial Virus and Mycoplasma pneumoniae in Pediatric Community-Acquired Lower Respiratory Tract Infections

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S265-S265
Author(s):  
Sanchit Kumar ◽  
Anita Chakravarti ◽  
Surinder Kumar ◽  
Seema Kapoor
Keyword(s):  
Respiratory Tract ◽  
Predictive Value ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Rt Pcr ◽  
Lower Respiratory Tract Infections ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

Abstract Background Respiratory syncytial virus (RSV) infection is a major cause of serious lower respiratory disease in infancy and early childhood and Mycoplasma pneumoniae (M. pneumoniae) is a common cause of respiratory tract infections in all age groups. This study was conducted to determine the role of RSV and M. pneumoniae and in pediatric lower respiratory tract infections employing serological tests, polymerase chain reaction (PCR) and reverse transcriptase PCR analysis. Methods In this prospective study, 75 children aged 1 month to 5 years with acute lower respiratory tract infections (LRTIs) were investigated. Paired serum samples were obtained on admission and after 4–6 weeks to assay for M. pneumonia antibodies. Nasopharyngeal aspirates were obtained for the detection of RSV antigen by using the immunochromatographic test, reverse transcriptase-polymerase chain reaction (RT-PCR) for RSV and M. pneumoniae by PCR. Results RSV infection was positive in 20(60.60%) children aged &lt;1 year and 13 (39.40%) aged 2–5 years, the difference being statistically insignificant (P = 0.360). M. pneumoniae infection was documented in a 15(57.6%) children aged &lt;1 year age and 11(42.4%) in age 2–5 years which was statistically significant(P = 0.026). Clinical and radiological features among RSV and M. pnemoniae positive and negative cases were comparable. Thirty (40%) children were positive for RSV antigen and by RT-PCR and 3(12%) only by RT-PCR. Serological evidence of M pneumoniae infection was documented in 24(32%) children. M. pnemoniae PCR was positive in 8 (10.66%) patients. Together, serology and PCR detected M. pneumoniae in 26(34.66%) children. Considering RT-PCR as a diagnostic standard, the sensitivity of RSV antigen by immunochromatography was 90.90%, specificity 100%, positive predictive value 100% and a negative predictive value of 93.3%.The sensitivity of M. pneumoniae serology was 75%, specificity 73.3%, positive predictive value 25% and a negative predictive value of 96% considering PCR as a diagnostic standard,. Conclusion Our data underline the role of RSV and M. pneumoniae as the major cause of community-acquired lower respiratory tract infections in children aged &lt;5 years. Disclosures All authors: No reported disclosures.

scholarly journals Statin-mediated disruption of Rho GTPase prenylation and activity inhibits respiratory syncytial virus infection

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Manpreet Malhi ◽  
Michael J. Norris ◽  
Wenming Duan ◽  
Theo J. Moraes ◽  
Jason T. Maynes
Keyword(s):  
Respiratory Syncytial Virus ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Surface Expression ◽  
Functional Enrichment ◽  
Host Protein ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Infections

AbstractRespiratory syncytial virus (RSV) is a leading cause of severe respiratory tract infections in children. To uncover new antiviral therapies, we developed a live cell-based high content screening approach for rapid identification of RSV inhibitors and characterized five drug classes which inhibit the virus. Among the molecular targets for each hit, there was a strong functional enrichment in lipid metabolic pathways. Modulation of lipid metabolites by statins, a key hit from our screen, decreases the production of infectious virus through a combination of cholesterol and isoprenoid-mediated effects. Notably, RSV infection globally upregulates host protein prenylation, including the prenylation of Rho GTPases. Treatment by statins or perillyl alcohol, a geranylgeranyltransferase inhibitor, reduces infection in vitro. Of the Rho GTPases assayed in our study, a loss in Rac1 activity strongly inhibits the virus through a decrease in F protein surface expression. Our findings provide new insight into the importance of host lipid metabolism to RSV infection and highlight geranylgeranyltransferases as an antiviral target for therapeutic development.

scholarly journals Bronchopulmonary Disposition of the Ketolide Telithromycin (HMR 3647)

2001 ◽  
Vol 45 (11) ◽  
pp. 3104-3108 ◽  
Author(s):  
Claudette Muller-Serieys ◽  
Paul Soler ◽  
Cathy Cantalloube ◽  
Françoise Lemaitre ◽  
Hai Pham Gia ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Alveolar Macrophages ◽  
Respiratory Tract Infections ◽  
Test Organism ◽  
Fiberoptic Bronchoscopy ◽  
Pharmacokinetic Profile ◽  
Diffusion Method ◽  
Median Concentration ◽  
Tract Infections

ABSTRACT Telithromycin (HMR 3647) is the first member of a new family of antimicrobials, the ketolides, developed specifically for the treatment of community-acquired respiratory tract infections. Telithromycin has proven in vitro activity against both common and atypical respiratory tract pathogens. The penetration of telithromycin into bronchopulmonary tissues and subsequent elimination from these sites were evaluated in four groups (groups A, B, C, and D) of six healthy male subjects who received telithromycin at 800 mg once daily for 5 days. Subjects in groups A, B, C, and D underwent fiberoptic bronchoscopy and bronchoalveolar lavage 2, 8, 24, and 48 h after receipt of the last dose, respectively. The concentration of telithromycin in the alveolar macrophages, epithelial lining fluid (ELF), and plasma was determined by the agar diffusion method with Bacillus subtilis ATCC 6633 as the test organism. The concentration of telithromycin in alveolar macrophages markedly exceeded that in plasma, reaching up to 146 times the concentration in plasma 8 h after dosing (median concentration, 81 mg/liter). Telithromycin was retained in alveolar macrophages 24 h after dosing (median concentration, 23 mg/liter), and it was still quantifiable 48 h after dosing (median concentration, 2.15 mg/liter). Telithromycin median concentrations in ELF also markedly exceeded concentrations in plasma (median concentration in ELF, 3.7 mg/liter 8 h after dosing). Telithromycin achieves high and sustained concentrations in ELF and in alveolar macrophages, while it maintains adequate levels in plasma, providing an ideal pharmacokinetic profile for effective treatment of community-acquired respiratory tract infections caused by either common or atypical, including intracellular, respiratory tract pathogens.

Sign in / Sign up

Export Citation Format

Share Document