scholarly journals Regulation and Function of Interferon-Lambda (IFNλ) and Its Receptor in Asthma

2021 ◽  
Vol 12 ◽  
Author(s):  
Susanne Krammer ◽  
Cristina Sicorschi Gutu ◽  
Janina C. Grund ◽  
Mircea T. Chiriac ◽  
Sabine Zirlik ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Ex Vivo ◽  
Chronic Respiratory Disease ◽  
The Body ◽  
Th2 Cells ◽  
Type Iii ◽  
Viral Spread ◽  
Interferon Lambda ◽  
Tract Infections

Asthma is a chronic respiratory disease affecting people of all ages, especially children, worldwide. Origins of asthma are suggested to be placed in early life with heterogeneous clinical presentation, severity and pathophysiology. Exacerbations of asthma disease can be triggered by many factors, including viral respiratory tract infections. Rhinovirus (RV) induced respiratory infections are the predominant cause of the common cold and also play a crucial role in asthma development and exacerbations. Rhinovirus mainly replicates in epithelial cells lining the upper and lower respiratory tract. Type III interferons, also known as interferon-lambda (IFNλ), are potent immune mediators of resolution of infectious diseases but they are known to be involved in autoimmune diseases as well. The protective role of type III IFNs in antiviral, antibacterial, antifungal and antiprotozoal functions is of major importance for our innate immune system. The IFNλ receptor (IFNλR) is expressed in selected types of cells like epithelial cells, thus orchestrating a specific immune response at the site of viruses and bacteria entry into the body. In asthma, IFNλ restricts the development of TH2 cells, which are induced in the airways of asthmatic patients. Several studies described type III IFNs as the predominant type of interferon increased after infection caused by respiratory viruses. It efficiently reduces viral replication, viral spread into the lungs and viral transmission from infected to naive individuals. Several reports showed that bronchial epithelial cells from asthmatic subjects have a deficient response of type III interferon after RV infection ex vivo. Toll like Receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) expressed on infectious agents, and induce the development of antiviral and antibacterial immunity. We recently discovered that activation of TLR7/8 resulted in enhanced IFNλ receptor mRNA expression in PBMCs of healthy and asthmatic children, opening new therapeutic frontiers for rhinovirus-induced asthma. This article reviews the recent advances of the literature on the regulated expression of type III Interferons and their receptor in association with rhinovirus infection in asthmatic subjects.

scholarly journals Respiratory tract infections in children with allergic asthma on allergen immunotherapy during influenza season

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuyun Li ◽  
Dongming Wang ◽  
Lili Zhi ◽  
Yunmei Zhu ◽  
Lan Qiao ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Allergic Asthma ◽  
Respiratory Tract Infections ◽  
Allergen Immunotherapy ◽  
Clinical Symptoms ◽  
Influenza Season ◽  
The Body ◽  
History Of ◽  
Tract Infections ◽  
Stage 1

AbstractTo describle how respiratory tract infections (RTIs) that occurred in children with allergic asthma (AA) on allergen immunotherapy (AIT) during an influenza season. Data including clinical symptoms and treatment history of children (those with AA on AIT and their siblings under 14 years old), who suffered from RTIs during an influenza season (Dec 1st, 2019–Dec 31st, 2019), were collected (by face to face interview and medical records) and analyzed. Children on AIT were divided into 2 groups: stage 1 (dose increasing stage) and stage 2 (dose maintenance stage). Their siblings were enrolled as control. During the study period, 49 children with AA on AIT (33 patients in stage 1 and 16 patients in stage 2) as well as 49 children without AA ( their siblings ) were included. There were no significant differences in occurrences of RTIs among the three groups (p > 0.05). Compared with children in the other two groups, patients with RTIs in stage 2 had less duration of coughing and needed less medicine. Children on AIT with maintenance doses had fewer symptoms and recovered quickly when they were attacked by RTIs, which suggested that AIT with dose maintenance may enhance disease resistance of the body.

scholarly journals Modern possibilities of herbal medicine in the treatment of acute inflammatory diseases of the upper respiratory tract

2021 ◽  
pp. 127-133
Author(s):  
A. V. Gurov ◽  
A. V. Muzhichkova
Keyword(s):  
Phenolic Compounds ◽  
Respiratory Tract ◽  
Inflammatory Diseases ◽  
The Body ◽  
Upper Respiratory Tract ◽  
Plant Materials ◽  
Pelargonium Sidoides ◽  
Medicinal Substances ◽  
Upper Respiratory ◽  
Tract Infections

The article provides data on the effectiveness of the use of the drug in the treatment of acute, chronic and recurrent diseases of the respiratory tract and ENT organs. The drug is an extract of Pelargonium sidoides. From the standpoint of modern pharmacology, it is known that the use of natural products based on plant materials ensures safety and the absence of pronounced side effects. The main active ingredients of pelargonium are phenolic compounds: coumarins, flavonoids and phenolic acids. The article details the biochemical and pharmacological properties of each of the above groups of compounds. It has been shown that the presence of several classes of phenolic compounds simultaneously contributes to the potentiation of the pharmacological effects of each group separately. Therefore, drug has a pronounced polytropic effect: antiviral, antibacterial, immunomodulatory, mucolytic, anti-inflammatory, antioxidant, cytoprotective. The article presents the results of numerous domestic and foreign randomized, placebo-controlled studies demonstrating its high efficacy and safety in the treatment of ENT diseases, upper respiratory tract infections and bronchitis, not only in adults, but also in children over 1 year old. On the basis of the analyzed and presented material, the authors concluded that the use of a natural-based drug in the treatment of acute respiratory infection is effective and safe, both as monotherapy and in combination with other medicinal substances. He is able to quickly eliminate not only the symptoms of inflammation, but also to support the body with any ailments of this type.

The In Vivo Source of Type I and Type III IFNs is Pathogen Dependent

2021 ◽  
Author(s):  
Marvin J. Sandoval ◽  
Hsiang-Chi Tseng ◽  
Heidi P. Risman ◽  
Sergey Smirnov ◽  
Qing Li ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Respiratory Tract ◽  
Influenza A ◽  
Influenza Infection ◽  
Type I ◽  
Protective Effects ◽  
Type Iii

Type I (-α, β) and type III (-λ) interferons (IFNs) are produced in response to virus infection and upregulate a largely overlapping set of IFN stimulated genes which mediate the protective effects of these antiviral cytokines. In vitro studies have demonstrated the redundancy of these two cytokine families which activate the same transcription factor, IFN stimulated gene factor 3 (ISGF3), via distinct ligands and receptors. However, in vivo, these IFN types do have distinct functions based on receptor distribution, but also ligand availability. Using a newly generated IFN-λ reporter mouse strain we have observed that both type I and type III IFNs are produced in response to respiratory tract infection by Newcastle disease virus (NDV) and influenza A virus (IAV). In the case of NDV these IFNs are synthesized by different cell types. Type I IFNs are produced primarily by alveolar macrophages, type III IFNs are made only by epithelial cells, and production of either is dependent on MAVS. While epithelial cells of the respiratory tract represent the primary target of IAV infection, we found that they did not significantly contribute to IFN-λ production, and IFN-λ protein levels were largely unaffected in the absence of MAVS. Instead we found that pDCs, a cell type known for robust IFN-α production via TLR/MyD88 signaling, were the major producers of IFN-λ during IAV infection, with pDC depletion during influenza infection resulting in significantly reduced levels of both IFN-α and IFN-λ. In addition, we were able to demonstrate that pDCs rely on type I IFN for optimal IFN-λ production. These studies therefore demonstrate that the in vivo producers of Type III IFNs in response to respiratory virus infection are pathogen dependent, a finding which may explain the varying levels of cytokine production induced by different viral pathogens.

Effects of pneumococcal vaccine in patients with chronic respiratory disease

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Cohort Study ◽  
Respiratory Tract ◽  
Respiratory Disease ◽  
Pneumococcal Vaccine ◽  
Pneumococcal Infection ◽  
Chronic Respiratory Disease ◽  
Case Control ◽  
Pneumococcal Vaccines ◽  
Tract Infections

When I started my PhD with my thesis entitled ‘‘Correlation ofQuantitative CT with selective alveolobronchogram andpulmonary function tests in emphysema’’ [1], the researchperformed in our dept was mainly focused on the pathogenesisand treatment of chronic obstructive pulmonary disease(COPD). Following my PhD, my further research focused oncontrol of breathing in patients with COPD [2, 3]. Part of myscientific work is the long-term observation of patients withchronic respiratory tract infection. In particular, I haveinvestigated the antibiotic resistance according to genotype ofpenicillin-binding protein and macrolide resistance genes ofStreptococcus peumoniae and Haemophilus influenzae isolatedfrom the patients with chronic respiratory diseases. I identifiedthe relationship between the emergence of resistant genes andthe risk factors of the patients. The pneumococcal vaccineincludes 23 purified capsular antigens, which covers 95% ofSTATEMENT OF INTEREST: None declared. the penicillin-nonsusceptible serotypes, and is expected toEur Respir Rev 2008; 17: 107, 43–45DOI: 10.1183/09059180.00010717Copyright?ERSJ Ltd 2008cEUROPEAN RESPIRATORY REVIEW VOLUME 17 NUMBER 107 43reduce the incidence of drug-resistant strains [4]. I thenfocused on the usefulness of the pneumococcal vaccine inpreventing either pneumonia or death in adults with chronicrespiratory disease and reducing penicillin-nonsusceptiblestrains.The percentage of respiratory tract infections caused bypneumococcus is particularly high among elderly patients.The currently available pneumococcal vaccine stimulates theformation of specific antibodies in vivo, resulting in theprevention of pneumococcal infection; the antibody specificto pneumococci is produced within 1 month of vaccinationand is retained in vivo for ,5 yrs. Among the studiesconducted to date to evaluate the effectiveness of pneumococcalvaccines, a placebo-controlled study involving mineworkers (known to have a high incidence of pneumococcalpneumonia, i.e. several percent or higher per year) and someother groups was performed in the 1970s. The study demonstratedthe effectiveness of vaccines against pneumonia andsepsis. In developed countries, however, it is very difficult todemonstrate the effectiveness of pneumococcal vaccines withthis type of study because the incidence of pneumococcalpneumonia is very low and .20,000 subjects need to beassigned to both the vaccinated group and the control(nonvaccinated group) for evaluation of effectiveness. In recentyears, the effectiveness of pneumococcal vaccines was studiedprimarily using case–control or indirect cohort study designs,demonstrating that vaccines are not useful in preventing theonset of nonbacteraemic pneumonia, but are for pneumococcalbacteraemia [5, 6]. In Japan, the percentage of people vaccinatedagainst pneumococcal infection is very low (2%), and itis difficult to perform a case–control study involving subjectswith pneumococcal infection, as is often done in developedcountries. In our cohort study, we were able to demonstrate theusefulness of vaccination despite the relatively small size of thepopulation studied. This probably owes much to the studydesign, i.e. the adoption of bacterial respiratory infection(which often complicates chronic respiratory disease) as anindicator of the effectiveness of vaccination and the techniqueof repeated measures analysis of variance, to compare thechange in the incidence of infection from the pre-vaccination tothe post-vaccination period between the vaccinated andnonvaccinated groups (fig. 1, table 1).

Bacterial lysates in the prevention of respiratory tract infections

2018 ◽  
Vol 72 (5) ◽  
pp. 1-8 ◽  
Author(s):  
Dariusz Jurkiewicz ◽  
Beata Zielnik-Jurkiewicz
Keyword(s):  
Respiratory Tract ◽  
Defense Mechanisms ◽  
Respiratory Tract Infections ◽  
Respiratory Infections ◽  
The Body ◽  
Bacterial Strains ◽  
Recurrent Respiratory Infections ◽  
Mucous Membranes ◽  
Bacterial Lysates ◽  
Tract Infections

Bacterial lysates stimulate the general immunity of the body in a non-specific way. They act on non-specific defense mechanisms, leading to an increase in type A antibody in mucous membranes, phagocytic activity and INF-ƴ production. They can also stimulate the production of specific antibodies against the bacterial antigens that make up the preparation. The oral immunomodulatory preparations with the best documented clinical efficacy available on the Polish market are Ismigen, Broncho-Vaxom, Ribomunyl and Luivac. They are all lysates of bacterial strains that most often cause respiratory tract infections. In many clinical trials, oral bacterial lysates have been shown to minimize the risk of recurrent respiratory infections in children and adults and reduce the need for antibiotics.

scholarly journals Macrolides Inhibit Fusobacterium nucleatum-Induced MUC5AC Production in Human Airway Epithelial Cells

2013 ◽  
Vol 57 (4) ◽  
pp. 1844-1849 ◽  
Author(s):  
Kentaro Nagaoka ◽  
Katsunori Yanagihara ◽  
Yosuke Harada ◽  
Koichi Yamada ◽  
Yohei Migiyama ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Respiratory Tract ◽  
Fusobacterium Nucleatum ◽  
Airway Epithelial Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Airway Epithelial ◽  
Content Type ◽  
Mucin Production ◽  
Tract Infections

ABSTRACTFusobacterium nucleatumis one of the most common anaerobic bacteria in periodontitis and is responsible for several extraoral infections, including respiratory tract diseases. In this study, we examined whetherF. nucleatuminduces mucin secretion in airway epithelial cells. We also examined the effects of macrolides onF. nucleatum-induced mucus production compared with the effects of other antibiotics that exert anti-anaerobic activities. The production of MUC5AC, the major core protein of mucin secreted from the airway surface epithelium, in bronchial epithelial cells after stimulation with culture supernatants (Sup) ofF. nucleatumwas analyzed by performing enzyme-linked immunosorbent assay and quantitative RT-PCR. The cell-signaling pathway ofF. nucleatumSup stimulation was also analyzed by Western blotting. For inhibition studies, cells were treated with azithromycin, clarithromycin, clindamycin (CLDM), and metronidazole (MTZ). TheF. nucleatumSup induced NCI-H292 cells to express MUC5AC at both the protein level and the mRNA level in both a time- and dose-dependent manner. Macrolides inhibitedF. nucleatumSup-induced MUC5AC production, while CLDM and MTZ were less effective.F. nucleatumSup induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), and this induction was suppressed by macrolides.F. nucleatumSup-induced MUC5AC production was blocked by the ERK pathway inhibitor U0126.F. nucleatumis likely to contribute to excessive mucin production, which suggests that periodontitis may correlate with the pathogenesis of chronic respiratory tract infection. Macrolides seem to reduce this mucin production and might represent an additional means of therapeutic intervention forF. nucleatumrespiratory tract infections other than CLDM and MTZ.

scholarly journals Importance of Type I and III Interferons at Respiratory and Intestinal Barrier Surfaces

2020 ◽  
Vol 11 ◽  
Author(s):  
Megan L. Stanifer ◽  
Cuncai Guo ◽  
Patricio Doldan ◽  
Steeve Boulant
Keyword(s):  
Epithelial Cells ◽  
Intestinal Barrier ◽  
The Body ◽  
Type I ◽  
Type I Ifn ◽  
Type Iii ◽  
Interferon Stimulated Genes ◽  
Mucosal Surfaces ◽  
Microbial Infections ◽  
Type Iii Ifn

Interferons (IFNs) constitute the first line of defense against microbial infections particularly against viruses. They provide antiviral properties to cells by inducing the expression of hundreds of genes known as interferon-stimulated genes (ISGs). The two most important IFNs that can be produced by virtually all cells in the body during intrinsic innate immune response belong to two distinct families: the type I and type III IFNs. The type I IFN receptor is ubiquitously expressed whereas the type III IFN receptor’s expression is limited to epithelial cells and a subset of immune cells. While originally considered to be redundant, type III IFNs have now been shown to play a unique role in protecting mucosal surfaces against pathogen challenges. The mucosal specific functions of type III IFN do not solely rely on the restricted epithelial expression of its receptor but also on the distinct means by which type III IFN mediates its anti-pathogen functions compared to the type I IFN. In this review we first provide a general overview on IFNs and present the similarities and differences in the signal transduction pathways leading to the expression of either type I or type III IFNs. By highlighting the current state-of-knowledge of the two archetypical mucosal surfaces (e.g. the respiratory and intestinal epitheliums), we present the differences in the signaling cascades used by type I and type III IFNs to uniquely induce the expression of ISGs. We then discuss in detail the role of each IFN in controlling pathogen infections in intestinal and respiratory epithelial cells. Finally, we provide our perspective on novel concepts in the field of IFN (stochasticity, response heterogeneity, cellular polarization/differentiation and tissue microenvironment) that we believe have implications in driving the differences between type I and III IFNs and could explain the preferences for type III IFNs at mucosal surfaces.

scholarly journals EspJ Is a Prophage-Carried Type III Effector Protein of Attaching and Effacing Pathogens That Modulates Infection Dynamics

2005 ◽  
Vol 73 (2) ◽  
pp. 679-686 ◽  
Author(s):  
Sivan Dahan ◽  
Siouxsie Wiles ◽  
Roberto M. La Ragione ◽  
Angus Best ◽  
Martin J. Woodward ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ex Vivo ◽  
Pathogen Transmission ◽  
Effector Proteins ◽  
In Vivo Studies ◽  
E Coli ◽  
Type Iii ◽  
Infection Dynamics ◽  
Enterocyte Effacement

ABSTRACT Enterohemorrhagic Escherichia coli, enteropathogenic E. coli, and Citrobacter rodentium are highly adapted enteropathogens that successfully colonize their host's gastrointestinal tract via the formation of attaching and effacing (A/E) lesions. These pathogens utilize a type III secretion system (TTSS) apparatus, encoded by the locus of enterocyte effacement, to translocate bacterial effector proteins into epithelial cells. Here, we report the identification of EspJ (E. coli-secreted protein J), a translocated TTSS effector that is carried on the 5′ end of the cryptic prophage CP-933U. Infection of epithelial cells in culture revealed that EspJ is not required for A/E lesion activity in vivo and ex vivo. However, in vivo studies performed with mice demonstrated that EspJ possesses properties that influence the dynamics of clearance of the pathogen from the host's intestinal tract, suggesting a role in host survival and pathogen transmission.

scholarly journals Klebsiella pneumoniae Yersiniabactin Promotes Respiratory Tract Infection through Evasion of Lipocalin 2

2011 ◽  
Vol 79 (8) ◽  
pp. 3309-3316 ◽  
Author(s):  
Michael A. Bachman ◽  
Jennifer E. Oyler ◽  
Samuel H. Burns ◽  
Mélissa Caza ◽  
François Lépine ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Respiratory Tract ◽  
Ex Vivo ◽  
Iron Acquisition ◽  
Opportunistic Pathogen ◽  
Respiratory Pathogen ◽  
Lipocalin 2 ◽  
Content Type ◽  
Tract Infections ◽  
Disseminated Disease

ABSTRACTKlebsiella pneumoniaeis a pathogen of increasing concern because of multidrug resistance, especially due toK. pneumoniaecarbapenemases (KPCs).K. pneumoniaemust acquire iron to replicate, and it utilizes iron-scavenging siderophores, such as enterobactin (Ent). The innate immune protein lipocalin 2 (Lcn2) is able to specifically bind Ent and disrupt iron acquisition. To determine whetherK. pneumoniaemust produce Lcn2-resistant siderophores to cause disease, we examined siderophore production by clinical isolates (n= 129) from respiratory, urine, blood, and stool samples and by defined siderophore mutants through genotyping and liquid chromatography-mass spectrometry. Three categories ofK. pneumoniaeisolates were identified: enterobactin positive (Ent+) (81%), enterobactin and yersiniabactin positive (Ent+Ybt+) (17%), and enterobactin and salmochelin (glycosylated Ent) positive (Ent+gly-Ent+) with or without Ybt (2%). Ent+Ybt+strains were significantly overrepresented among respiratory tract isolates (P= 0.0068) and β-lactam-resistant isolates (P= 0.0019), including the epidemic KPC-producing clone multilocus sequence type 258 (ST258). Inex vivogrowth assays, gly-Ent but not Ybt allowed evasion of Lcn2 in human serum, whereas siderophores were dispensable for growth in human urine. In a murine pneumonia model, an Ent+strain was an opportunistic pathogen that was completely inhibited by Lcn2 but caused severe, disseminated disease inLcn2−/−mice. In contrast, an Ent+Ybt+strain was a frank respiratory pathogen, causing pneumonia despite Lcn2. However, Lcn2 retained partial protection against disseminated disease. In summary, Ybt is a virulence factor that is prevalent among KPC-producingK. pneumoniaeisolates and promotes respiratory tract infections through evasion of Lcn2.

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