scholarly journals Streptococcus pneumoniae serotype 22F infection in respiratory syncytial virus infected neonatal lambs enhances morbidity

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0235026
Author(s):  
Sarhad Alnajjar ◽  
Panchan Sitthicharoenchai ◽  
Jack Gallup ◽  
Mark Ackermann ◽  
David Verhoeven
Keyword(s):  
Respiratory Syncytial Virus ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Clinical Symptoms ◽  
Dual Infection ◽  
Lesion Development ◽  
Viral Loads ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Neonatal Lambs

Respiratory syncytial virus (RSV) is the primary cause of viral bronchiolitis resulting in hospitalization and a frequent cause of secondary respiratory bacterial infection, especially by Streptococcus pneumoniae (Spn) in infants. While murine studies have demonstrated enhanced morbidity during a viral/bacterial co-infection, human meta-studies have conflicting results. Moreover, little knowledge about the pathogenesis of emerging Spn serotype 22F, especially the co-pathologies between RSV and Spn, is known. Here, colostrum-deprived neonate lambs were divided into four groups. Two of the groups were nebulized with RSV M37, and the other two groups were mock nebulized. At day three post-RSV infection, one RSV group (RSV/Spn) and one mock-nebulized group (Spn only) were inoculated with Spn intratracheally. At day six post-RSV infection, bacterial/viral loads were assessed along with histopathology and correlated with clinical symptoms. Lambs dually infected with RSV/Spn trended with higher RSV titers, but lower Spn. Additionally, lung lesions were observed to be more frequent in the RSV/Spn group characterized by increased interalveolar wall thickness accompanied by neutrophil and lymphocyte infiltration and higher myeloperoxidase. Despite lower Spn in lungs, co-infected lambs had more significant morbidity and histopathology, which correlated with a different cytokine response. Thus, enhanced disease severity during dual infection may be due to lesion development and altered immune responses rather than bacterial counts.

scholarly journals STREPTOCOCCUS PNEUMONIAE SEROTYPE 22F INFECTION IN RESPIRATORY SYNCYTIAL VIRUS INFECTED NEONATAL LAMBS ENHANCES MORBIDITY

2020 ◽  
Author(s):  
Sarhad Alnajjar ◽  
Panchan Sitthicharoenchai ◽  
Jack Gallup ◽  
Mark Ackermann ◽  
David Verhoeven
Keyword(s):  
Respiratory Syncytial Virus ◽  
Streptococcus Pneumoniae ◽  
Immune Responses ◽  
Post Infection ◽  
Clinical Symptoms ◽  
Dual Infection ◽  
Lesion Development ◽  
Viral Loads ◽  
Syncytial Virus ◽  
Neonatal Lambs

AbstractRespiratory syncytial virus (RSV) is the primary cause of viral bronchiolitis resulting in hospitalization and a frequent cause of secondary respiratory bacterial infection, especially by Streptococcus pneumoniae (Spn) in infants. While murine studies have demonstrated enhanced morbidity during a viral/bacterial co-infection, human meta-studies have conflicting results. Moreover, little knowledge about the pathogenesis of emerging Spn serotype 22F, and especially the co-pathologies between RSV and Spn is known. Here, colostrum-deprived neonate lambs were divided into four groups. Two of the groups were nebulized with RSV M37, and the other two groups mock nebulized. At day 3 post-infection, one RSV group (RSV/Spn) and one mock-nebulized group (Spn only) were inoculated with Spn intratracheally. At day 6 post-infection, bacterial/viral loads were assessed along with histopathology and correlated with clinical symptoms. Lambs dually infected with RSV/Spn had higher RSV titers, but lower Spn. Additionally, lung lesions were observed to be more intense in the RSV/Spn group characterized by increased interalveolar wall thickness accompanied by neutrophil and lymphocyte infiltration. Despite lower Spn in lungs, co-infected lambs had more significant morbidity and histopathology, which correlated with a different cytokine response. Thus, enhanced disease severity during dual infection may be due to lesion development and altered immune responses rather than bacterial counts.

scholarly journals The Role of Toll-like receptor 4 in respiratory syncytial virus replication, interferon lambda 1 induction, and chemokine responses

2018 ◽  
Author(s):  
Lindsay Broadbent ◽  
Jonathon D. Coey ◽  
Michael D. Shields ◽  
Ultan F. Power
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Virus Replication ◽  
Growth Kinetics ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Pro Inflammatory Cytokines

AbstractRespiratory syncytial virus (RSV) infection is the leading cause of severe lower respiratory tract infections (LRTI) in infants worldwide. The immune responses to RSV infection are implicated in RSV pathogenesis but RSV immunopathogenesis in humans remains poorly understood. We previously demonstrated that IFN-λ1 is the principle interferon induced following RSV infection of infants and well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). Interestingly, RSV F interacts with the TLR4/CD14/MD2 complex to initiate secretion of pro-inflammatory cytokines, while TLR4 stimulation with house dust mite induces IFN-λ1 production. However, the role of TLR4 in RSV infection and concomitant IFN-λ1 induction remains unclear. Using our RSV/WD-PBEC infection model, we found that CLI-095 inhibition of TLR4 resulted in significantly reduced viral growth kinetics, and secretion of IFN-λ1 and pro-inflammatory chemokines. To elucidate specific TLR4 signalling intermediates implicated in virus replication and innate immune responses we selected 4 inhibitors, including LY294002, U0126, SB203580 and JSH-23. SB203580, a p38 MAPK inhibitor, reduced both viral growth kinetics and IFN-λ1 secretion, while JSH-23, an NF-κB inhibitor, reduced IFN-λ1 secretion without affecting virus growth kinetics. Our data indicate that TLR4 plays a role in RSV entry and/or replication and IFN-λ1 induction following RSV infection is mediated, in part, by TLR4 signalling through NF- κB and/or p38 MAPK. Therefore, targeting TLR4 or downstream effector proteins could present novel treatment strategies against RSV.ImportanceThe role of TLR4 in RSV infection and IFN-λ1 induction is controversial. Using our WD-PBEC model, which replicates many hallmarks of RSV infection in vivo, we demonstrated that the TLR4 pathway is involved in both RSV infection and/or replication and the concomitant induction of IFN-λ1 and other pro-inflammatory cytokines. Increasing our understanding of the role of TLR4 in RSV immunopathogenesis may lead to the development of novel RSV therapeutics.

Respiratory Syncytial Virus (RSV) Infections in Immunocompromized Children.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5300-5300
Author(s):  
Alan Kwok Shing Chiang ◽  
Godfrey Chi Fung Chan ◽  
Shau Yin Ha ◽  
Kwok Hung Chan
Keyword(s):  
Respiratory Syncytial Virus ◽  
Clinical Symptoms ◽  
Bone Marrow Failure ◽  
Severe Pneumonia ◽  
Viral Clearance ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Individual ◽  
Tract Infections ◽  
Oncology Unit

Abstract Eleven children who were immunocompromized due to chemotherapy were infected with respiratory syncytial virus (RSV) during an outbreak of RSV infection in the Pediatric Oncology Unit of Queen Mary Hospital, The University of Hong Kong. The clinical symptoms, effect on treatment regimen, outcome of infection and viral clearance had been followed prospectively in all 11 children. Viral clearance was documented by immunofluorescence and PCR studies of nasopharyngeal aspirates or nasal/throat swabs. Eight of the 11 children had upper respiratory symptoms with the remaining 3 patients progressing to lower respiratory tract infections (LRTI). All except one had protracted viral symptoms but eventually recovered without the need for specific anti-viral treatment or intensive support. However, the chemotherapy regimen or scheduled BMT had been significantly interrupted. One patient developed progressively severe pneumonia which was further complicated by adenovirus reactivation causing bone marrow failure and severe sepsis resulting in death of this patient. The viral clearance of RSV was delayed in all patients with median of 20 days (range 9–81 days). One patient had recurrence of RSV detected by PCR 35 days after intial documentation of clearance, after a BMT procedure. The delayed viral clearance correlated with protracted viral symptoms. In conclusion, RSV clearance is delayed in immunocompromized hosts causing protracted viral symptoms, progression to LRTI and interruption to chemotherapy treatment. The delay in viral clearance appears proportional to the degree of immunosuppression of the individual.

scholarly journals A Comparison of Respiratory Syncytial Virus (RSV) Viral Loads Between Nasopharyngeal and Mid-Turbinate Swabs From Children <24 Months With RSV Infection

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Anne J. Blaschke ◽  
Matthew McKevitt ◽  
Krow Ampofo ◽  
Tammi Lewis ◽  
Ying Guo ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Viral Loads ◽  
Rsv Infection ◽  
Syncytial Virus

scholarly journals Transient Neutropenia in Immunocompetent Infants with Respiratory Syncytial Virus Infection

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 301
Author(s):  
Tatsuya Korematsu ◽  
Hiroshi Koga
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Streptococcus Pneumoniae ◽  
Moraxella Catarrhalis ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Serious Infection ◽  
Hematological Disorder ◽  
Rsv Infection ◽  
Syncytial Virus

The incidence of neutropenia and the association between neutropenia and severity of respiratory symptoms among infants with respiratory syncytial virus (RSV) infections remain to be elucidated. This single-center, retrospective study included immunocompetent infants (<10 months old) with laboratory-confirmed RSV infection admitted to our center between January 2012 and December 2019. Incidence of neutropenia (<1.0 × 109/L) within 10 days of onset and risk factors associated with subsequent neutropenia were evaluated. Among the 292 infants with RSV infection, including 232 (79%) with mild infection, neutropenia was observed in 31 (11%), with severe neutropenia (<0.5 × 109/L) in 3 (1.0%). No neutropenic infants developed serious infection or hematological disorder. Infants without neutropenia showed age <3 months at onset in 34%, C-reactive protein level <1.0 mg/L in 27%, and nasopharyngeal microbiota composition with any of Moraxella catarrhalis, Streptococcus pneumoniae, or Haemophilus influenzae in 63%. In comparison, infants with neutropenia showed age <3 months at onset in 74% (relative risk [RR] 2.15; 95% confidence interval [CI] 1.65–2.81), C-reactive protein level <1.0 mg/L in 55% (RR 2.02; 95% CI 1.38–2.94), and microbiota including Moraxella catarrhalis, Streptococcus pneumoniae, or Haemophilus influenzae in 15% (RR 0.24; 95% CI 0.10–0.61). Multiple logistic regression analyses showed that younger age at onset and absence of that nasopharyngeal microbiota profile were associated with development of neutropenia. In conclusion, age and airway microbiota are considered as risk factors for the development of transient neutropenia among infants with RSV infection. However, the neutropenia seems not to develop serious infection or hematological disorder.

scholarly journals Contribution of Dendritic Cells in Protective Immunity against Respiratory Syncytial Virus Infection

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 102 ◽  
Author(s):  
Hi Eun Jung ◽  
Tae Hoon Kim ◽  
Heung Kyu Lee
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Defense Mechanisms ◽  
Adaptive Immune Response ◽  
The Elderly ◽  
Effective Vaccine ◽  
Adaptive Immune ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. The socioeconomic burden of RSV infection is substantial because it leads to serious respiratory problems, subsequent hospitalization, and mortality. Despite its clinical significance, a safe and effective vaccine is not yet available to prevent RSV infection. Upon RSV infection, lung dendritic cells (DCs) detecting pathogens migrate to the lymph nodes and activate the adaptive immune response. Therefore, RSV has evolved various immunomodulatory strategies to inhibit DC function. Due to the capacity of RSV to modulate defense mechanisms in hosts, RSV infection results in inappropriate activation of immune responses resulting in immunopathology and frequent reinfection throughout life. This review discusses how DCs recognize invading RSV and induce adaptive immune responses, as well as the regulatory mechanisms mediated by RSV to disrupt DC functions and ultimately avoid host defenses.

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