scholarly journals Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage

2018 ◽  
Author(s):  
Simon P. Jochems ◽  
Fernando Marcon ◽  
Beatriz F. Carniel ◽  
Mark Holloway ◽  
Elena Mitsi ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Bacterial Pneumonia ◽  
Influenza Infection ◽  
Upper Respiratory Tract ◽  
Pneumococcal Carriage ◽  
Genome Wide ◽  
Immunological Mechanisms ◽  
Upper Respiratory ◽  
Live Attenuated Influenza Virus ◽  
Secondary Bacterial Pneumonia

AbstractSecondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.

scholarly journals Examining the Executioners, Influenza Associated Secondary Bacterial Pneumonia

2021 ◽  
Author(s):  
Timothy R. Borgogna ◽  
Jovanka M. Voyich
Keyword(s):  
Streptococcus Pyogenes ◽  
Bacterial Pneumonia ◽  
Influenza Infection ◽  
Mortality Rates ◽  
Upper Respiratory Tract ◽  
Influenza Pandemics ◽  
Upper Respiratory ◽  
Bacterial Sensing ◽  
Secondary Bacterial Pneumonia ◽  
Increased Susceptibility

Influenza infections typically present mild to moderate morbidities in immunocompetent host and are often resolved within 14 days of infection onset. Death from influenza infection alone is uncommon; however, antecedent influenza infection often leads to an increased susceptibility to secondary bacterial pneumonia. Bacterial pneumonia following viral infection exhibits mortality rates greater than 10-fold of those of influenza alone. Furthermore, bacterial pneumonia has been identified as the major contributor to mortality during each of the previous four influenza pandemics. Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pyogenes are the most prevalent participants in this pathology. Of note, these lung pathogens are frequently found as commensals of the upper respiratory tract. Herein we describe influenza-induced host-changes that lead to increased susceptibility to bacterial pneumonia, review virulence strategies employed by the most prevalent secondary bacterial pneumonia species, and highlight recent findings of bacterial sensing and responding to the influenza infected environment.

scholarly journals The study of neuraminidase immunity in protection against secondary bacterial pneumonia induced by S. aureus after influenza infection in mice

2021 ◽  
Vol 97 (6) ◽  
pp. 564-577
Author(s):  
I. A. Leneva ◽  
I. N. Falynskova ◽  
N. P. Kartashova ◽  
E. A. Glubokova ◽  
A. V. Poddubikov ◽  
...  
Keyword(s):  
Weight Loss ◽  
Influenza Virus ◽  
Bacterial Pneumonia ◽  
Bacterial Infections ◽  
Influenza Infection ◽  
H1n1 Influenza ◽  
H1n1 Influenza Virus ◽  
Virus Challenge ◽  
Influenza Outbreaks ◽  
Secondary Bacterial Pneumonia

Introduction. Pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. We previously have shown that vaccination with Virus-like particles (VLPs) containing hemagglutinin (HA) of influenza virus reduces mortality caused by bacterial infections after an influenza infections in mice.The aim of this work is to study whether this protective effect may be potentiated by supplementing the HA preparation with the influenza neuraminidase (NA).Materials and methods. We studied the effect of Gag-VLPs with the influenza HA or NA from А/PR/8/34 alone or in combination, in a lethal BALB/c mouse model of S. aureus infection after vaccine-matched or mismatched influenza virus challenge.Results. A cocktail of HA-Gag and NA-Gag-VLPs fully protected from weight loss, mortality and viral replication and significantly reduced the bacterial burden in the lungs of А/PR/8/34 infected animals. Immunization with this cocktail HA-Gag-VLPs 100 ng + NA-Gag-VLPs 20 ng also protected 60% of animals from mortality associated with secondary bacterial S. aureus infection following a heterologous H1N1 influenza virus challenge, and led to the significant protection from weight loss and pulmonary pathogen replication even in the absence of HA-inhibition and NA-inhibition antibodies.Conclusion. Our results indicate that influenza vaccination may improve the outcome of a secondary bacterial pneumonia induced by S. aureus after influenza even when the virus is antigenically different from the vaccine strain. At the same time, in our model, the significance of the immunity to influenza virus HA was prevalent.

scholarly journals Vaccination with virus-like particles containing hemagglutinin protects the lungs of mice with postifluenza bacterial pneumonia: virological, microbiological and clinical data

2020 ◽  
Vol 65 (3) ◽  
pp. 150-158
Author(s):  
I. N. Falynskova ◽  
A. Yu. Egorov ◽  
A. V. Poddubikov ◽  
N. O. Vartanova ◽  
N. P. Kartashova ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Clinical Data ◽  
Murine Model ◽  
Bacterial Pneumonia ◽  
Influenza Infection ◽  
Viral Disease ◽  
Influenza Viruses ◽  
Lung Damage ◽  
Virus Like Particles ◽  
Secondary Bacterial Pneumonia

Introduction. Influenza is a severe viral disease, a frequent complication of which is a secondary bacterial pneumonia. Influenza vaccines prevent secondary bacterial complications. Virus-like particles are one of the promising areas for the development of new vaccines. The aim of this work is to study the correlation of the pathomorphological characteristics of the lungs with clinical, virological, and microbiological markers of the disease at vaccination with virus-like particles (VLPs), containing hemagglutinin (HA) of influenza virus (HA-Gag-VLPs) in a murine model of secondary bacterial pneumonia induced by S. pneumoniae after influenza infection. Material and methods. BALB/c mice were vaccinated with VLPs containing influenza HA. After 21 days, mice were infected with two strains of influenza viruses, homologous and non-homologous, and 5 days after viral infection, were infected with S. pneumoniae. The vaccination effect was evaluated by morphological, virological (titer of the virus in the lungs) and microbiological (titer of bacteria in the lungs) data, and was confirmed by clinical data (survival, change in body weight). Results. Immunization with HA-Gag-VLPs, followed by infection with a homologous influenza virus and S. pneumoniae, reduced the area of foci of inflammation, inhibited the replication of the virus and bacteria in the lungs, and also protected animals from death and reduced their weight loss. Immunization with HA-Gag-VLPs upon infection with a heterologous strain and S. pneumoniae did not affect these criteria. Conclusion. The immunization with HA-Gag-VLPs prevented the viral replication, providing a reduction of S. pneumoniae titer and the degree of lung damage, protecting animals from the disease in a murine model of secondary bacterial pneumonia, induced by S. pneumoniae, after influenza infection with homologous strain of the virus.

scholarly journals Clinical and immunological changes in patients with chronic inflammatory diseases of the upper respiratory tract at different periods after administration of influenza vaccine. Message 1. The influence of parenteral influenza vaccination on the clinical condition and indicators of systemic humoral immunity in patients with chronic inflammatory diseases of the upper respiratory tract

2021 ◽  
pp. 4-11
Author(s):  
Dmitry I. Zabolotny ◽  
Oleg F. Melnikov ◽  
Sergei V. Timchenko ◽  
Oksana G. Rylska ◽  
Inna V. Faraon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Influenza Vaccination ◽  
Clinical Condition ◽  
Inflammatory Diseases ◽  
Influenza Infection ◽  
Upper Respiratory Tract ◽  
Total Ige ◽  
Chronic Inflammatory Diseases ◽  
Upper Respiratory

Topicality: Today, as an assessment of the effectiveness of vaccination against influenza infection is to determine the level of antibodies against influenza virus hemagglutinin, which is determined by the reaction of inhibition of hemagglutination. It is known that the effect of vaccination with modern drugs is short-lived, compared with what remains after the disease. Therefore, there is a need for further vaccinations, which are carried out without taking into account the state of immunity in those who will be vaccinated. This raises the question of the appropriateness of this approach in individuals who, according to this indicator, can already be considered protected from influenza infection and how often such patients occur in clinical practice. Material and methods: From the autumn-winter period of 2019 to November 2020, 32 donors and 32 patients with chronic inflammatory diseases of the upper respiratory tract chronic inflammatory diseases of the upper respiratory tract of both sexes who were not vaccinated for 1 year before the study were examined. Among these patients, 11 were diagnosed with chronic rhinosinusitis, 9 with chronic tonsillitis, and 12 with chronic pharyngitis. All patients with chronic inflammatory diseases of the upper respiratory tract underwent a complete otolaryngological examination prior to influenza vaccination and were monitored for another 36 weeks thereafter. Attention was paid to their general clinical condition, cases of exacerbations of chronic inflammatory diseases of the upper respiratory tract and the number of episodes of acute respiratory viral infections during the year before vaccination according to the anamnesis and for the observation period during the post-vaccination period. Samples of serum venous blood of donors, as well as persons with chronic inflammatory diseases of the upper respiratory tract were obtained at the initial examination, and in vaccinated patients 3, 12 and 36 weeks after vaccination and stored at -20°C (Ardo, Italy) until the simultaneous detection of antibodies (Ab) to influenza A and B viruses by hemagglutination inhibition reaction with human erythrocytes 0 group. Trivalent influenza inactivated split vaccine Vaxigrip (France) was used both for vaccination and in the determination of Ab in the blood for influenza viruses. In all examinations, the titer of anti-influenza Ab and the content of immune complexes were determined in the sera of patients, and the content of total IgE was measured in patients with chronic inflammatory diseases of the upper respiratory tract before and after 12 and 36 weeks. Statistical processing of the obtained results was performed in accordance with the recommendations of Glantz. Results: In 41% of those examined protectively significant titers of antibodies to hemagglutinins of vaccine strains of influenza virus vaccine Vaxigrip were detected in the blood. Parenteral vaccination of patients with chronic inflammatory diseases of the upper respiratory tract against influenza helped to improve the course of their underlying clinical disease and reduce their incidence of acute respiratory viral infections within 36 weeks after vaccination. The effect of increasing the level of antibodies to hemagglutinins of influenza virus remained at the limit of 3 months and decreased. Influenza vaccination in patients with chronic inflammatory diseases of the upper respiratory tract with the presence of most of them at the time of vaccination of clinically significant protective titers of antibodies to hemagglutinins vaccine strains of viruses led to an increase in blood in the long term of the vaccination process levels of immune complex and total IgE relative to their initial level, while these indicators did not exceed the limits of their physiological values. Conclusion: Single parenteral influenza vaccination leads to a short-term increase in the blood of specific projective antibodies, improving the clinical condition of patients with inflammatory diseases of the upper respiratory tract, increasing the level of immune complexes and total IgE.

scholarly journals Efficacy of an experimental drug based on technologically processed antibodies in models of influenza infection and secondary bacterial pneumonia: Results of a preclinical study

2020 ◽  
pp. 55-63
Author(s):  
Н.В. Петрова ◽  
А.Г. Емельянова ◽  
С.А. Тарасов ◽  
Н. П. Карташова ◽  
Е.А. Глубокова
Keyword(s):  
Survival Rate ◽  
Bacterial Pneumonia ◽  
Influenza Infection ◽  
Control Groups ◽  
Mhc I ◽  
Mhc Ii ◽  
Cd4 Receptor ◽  
2009 H1n1 ◽  
Secondary Bacterial Pneumonia ◽  
Complex Drug

Целью исследования была оценка противовирусной активности экспериментальных образцов сверхвысоких разведений антител к различным мишеням, вовлеченным в реакции иммунного ответа (MHC I, MHC II, CD4 рецептор, ИФН-γ). Методы. Исследование противовирусной активности сверхвысоких разведений антител к молекуле MHC I проводили на модели летальной гриппозной инфекции (грипп А/Калифорния/04/2009 (H1N1)pdm09), тогда как протективный эффект комплексного препарата, содержащего сверхвысокие разведения антител к молекулам MHC I, MHC II, ИФН-γ и к CD4 рецептору, оценивали на модели смешанной вирусно-бактериальной пневмонии (последовательное инфицирование вирусом гриппа А/Калифорния/04/2009 (H1N1) и Staphylococcus aureus). Результаты. Показано, что сверхвысокие разведения антител к MHC I увеличивали выживаемость животных в эксперименте на 46,7% и 52,4% по сравнению с группами отрицательного контроля и плацебо (p < 0,05), соответственно. Препарат сравнения Осельтамивир повышал этот же показатель на 60% и 85,7% по сравнению с теми же группами животных (p < 0,05). На модели смешанной вирусно-бактериальной инфекции комплексный препарат повышал выживаемость мышей на 30% и 40% (p < 0,05) относительно контрольных групп. Введение Осельтамивира в комбинации с Цефуроксимом выражалось в увеличении выживаемости животных на 50% и 60%, соответственно. Статистически значимого снижения вирусной или бактериальной нагрузки ни для одной из групп выявлено не было. Заключение. Впервые продемонстрирована эффективность экспериментальных препаратов, содержащих сверхвысокие разведения антител к молекуле MHC I, а также их комплекс к MHC I, MHC II, ИФН-γ и к CD4 рецептору в моделях гриппозной инфекции и вирусно-бактериальной пневмонии у животных. Полученные данные свидетельствуют о перспективности дальнейшего изучения протективных эффектов данных образцов при вирусных и бактериальных инфекциях. The aim of this study was to evaluate the antiviral activity of ultra-highly diluted antibodies to various targets (MHC I, MHС II, INFg, and CD4 receptor) involved in the immune response. Methods. The antiviral activity of ultra-highly diluted antibodies to the MHC I molecule was evaluated in a standard model of the lethal A/California/04/2009 (H1N1)pdm09 influenza infection, and the protective effect of a complex drug containing highly diluted antibodies to MHC I and MHC II molecules, INFg, and CD4 receptor was accessed in a model of secondary bacterial pneumonia (A/California/04/2009 (H1N1) influenza virus challenge followed by Staphylococcus aureus inoculation). Results. The treatment with ultra-highly diluted antibodies to MHC I increased the survival rate of mice by 46.7% and 52.4% vs. the negative control and placebo groups (p < 0.05), respectively. The survival rate was increased in the Oseltamivir group by 60% and 85.7% vs. the same control groups (p < 0.05). In the model of secondary bacterial pneumonia following influenza, the complex drug increased the survival rate of mice by 30% and 40% (p < 0.05) vs. the control groups. The combined application of Oseltamivir and Cefuroxime increased the survival rate by 50% and 60%, respectively. There was no statistically significant decrease in the viral or bacterial load in any of the groups. Conclusion. The study showed for the first time that highly diluted antibodies to the MHC I molecule as well as the complex drug containing highly diluted antibodies to MHC I, MHС II, INFg, and CD4 receptor were effective in animal models of influenza infection and secondary bacterial pneumonia. Further investigation of protective effects of these samples in viral and bacterial infections is promising.

scholarly journals Increased Acid Stability of the Hemagglutinin Protein Enhances H5N1 Influenza Virus Growth in the Upper Respiratory Tract but Is Insufficient for Transmission in Ferrets

2013 ◽  
Vol 87 (17) ◽  
pp. 9911-9922 ◽  
Author(s):  
H. Zaraket ◽  
O. A. Bridges ◽  
S. Duan ◽  
T. Baranovich ◽  
S.-W. Yoon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Tract ◽  
Upper Respiratory Tract ◽  
H5n1 Influenza Virus ◽  
Acid Stability ◽  
Virus Growth ◽  
H5n1 Influenza ◽  
Hemagglutinin Protein ◽  
Upper Respiratory

Quercetin reduces susceptibility to influenza infection following stressful exercise

2008 ◽  
Vol 295 (2) ◽  
pp. R505-R509 ◽  
Author(s):  
J. M. Davis ◽  
E. A. Murphy ◽  
J. L. McClellan ◽  
M. D. Carmichael ◽  
J. D. Gangemi
Keyword(s):  
Influenza Virus ◽  
Symptom Severity ◽  
Fruits And Vegetables ◽  
Influenza Infection ◽  
Exercise Stress ◽  
Upper Respiratory Tract ◽  
Time To Death ◽  
Susceptibility To Infection ◽  
Increased Risk ◽  
The Impact

Exercise stress is associated with increased risk for upper respiratory tract infection. We have shown that exercise stress can increase susceptibility to infection. Quercetin, a flavonoid present in a wide variety of fruits and vegetables, has been reported to inhibit infectivity and replication of a broad spectrum of viruses and may offset the increase in susceptibility to infection associated with stressful exercise. This study examined the effects of quercetin feedings on susceptibility to the influenza virus A/Puerto Rico/8/34 (H1N1) following stressful exercise. Mice were randomly assigned to one of four treatment groups: exercise-placebo, exercise-quercetin, control-placebo, or control-quercetin. Exercise consisted of a run to fatigue (∼140 min) on a treadmill for 3 consecutive days. Quercetin (12.5 mg/kg) was administered via gavage for 7 days before viral challenge. At 30 min after the last bout of exercise or rest, mice ( n = 23–30) were intranasally inoculated with a standardized dose of influenza virus (0.04 hemagglutinating units). Mice were monitored daily for morbidity (time to sickness), symptom severity, and mortality (time to death) for 21 days. Exercise stress was associated with an increased susceptibility to infection [morbidity, mortality, and symptom severity on days 5–7 ( P < 0.05)]; quercetin offset the increase in susceptibility to infection [morbidity, mortality, and symptom severity on days 5–7 ( P < 0.05)] that was associated with stressful exercise. These data suggest that short-term quercetin feedings may prove to be an effective strategy to lessen the impact of stressful exercise on susceptibility to respiratory infection.

scholarly journals GRANULOMATOSIS WITH POLYANGIITIS: TREAT THE PATIENT NOT SYMPTOMS

2018 ◽  
Keyword(s):  
Granulomatosis With Polyangiitis ◽  
Treatment Strategies ◽  
Granulomatous Inflammation ◽  
Organ Damage ◽  
Upper Respiratory Tract ◽  
Childbearing Age ◽  
Immunological Mechanisms ◽  
Upper Respiratory ◽  
Tract Infections ◽  
In Pregnancy

Immunological mechanisms of appearance and therapeutic treatment strategies were discussed on example of the rare granulomatosis with polyangiitis clinical case in young patient. This vasculitis, formerly known as Wegener’s granulomatosis, is a rare multisystem autoimmune disease with necrotizing granulomatous inflammation and pauci-immune vasculitis in small- and medium-sized blood vessels. Autoimmune diseases affect 5 to 7% of people, are commoner in women of childbearing age, and are frequently encountered in pregnancy. They may remit or improve during pregnancy, butcan flare or present in pregnancy with disastrous consequences. Otorhinolaryngologist is the first physician to contact for the majority of patients with GPA. This diagnosis must always be taken into consideration in patients with recurrent upper respiratory tract infections, otitis, mucosal ulcers and laryngitis. Proper and early diagnosis is crucial for imminent therapy implementation and allows avoiding irreversible organ damage.

scholarly journals Microbiome disturbance and resilience dynamics of the upper respiratory tract in response to influenza A virus infection in humans and ferrets

2018 ◽  
Author(s):  
Drishti Kaul ◽  
Raveen Rathnasinghe ◽  
Marcela Ferres ◽  
Gene S. Tan ◽  
Aldo Barrera ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Influenza A Virus ◽  
Influenza A ◽  
Cellular Damage ◽  
Upper Respiratory Tract ◽  
Upper Respiratory ◽  
Influenza A Virus Infection ◽  
Over Time

AbstractInfection with influenza can be aggravated by bacterial co-infections, which often results in disease exacerbation because of host responses and cellular damage. The native upper respiratory tract (URT) microbiome likely plays a role, yet the effects of influenza infection on the URT microbiome are largely unknown. We performed a longitudinal study to assess the temporal dynamics of the URT microbiomes of uninfected and influenza virus-infected humans and ferrets. Uninfected human patients and ferret URT microbiomes had stable “heathy ecostate” communities both within and between individuals. In contrast, infected patients and ferrets exhibited large changes in bacterial community composition over time and between individuals. The “unhealthy” ecostates of infected individuals progressed towards the “healthy ecostate” over time, coinciding with viral clearance and recovery. Blooms of Pseudomonas were a statistically associated constant in the disturbed microbiomes of infected individuals. The dynamic and resilient nature of the microbiome during influenza virus infection in multiple hosts provides a compelling rationale for the maintenance of the microbiome homeostasis as a potential therapeutic target to prevent IAV associated bacterial co-infections.One Sentence SummaryDynamics of the upper respiratory tract microbiome during influenza A virus infection

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