scholarly journals Polymorphisms of Toll Like Receptors in the Genetics of Severe RSV Associated Diseases

2008 ◽  
Vol 25 (1) ◽  
pp. 59-65 ◽  
Author(s):  
Beena Mailaparambil ◽  
Marcus Krueger ◽  
Jessica Heinze ◽  
Johannes Forster ◽  
Andrea Heinzmann
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Trend Test ◽  
Toll Like Receptors ◽  
Major Health Problem ◽  
Associated Diseases ◽  
Wide Range ◽  
Rsv Infection ◽  
Syncytial Virus

Toll like receptors (TLRs) are an essential part of the innate immune response. So far, ten different TLRs were identified in humans. They recognize a wide range of microbial and viral pathogens. Infection by respiratory syncytial virus (RSV) is still a major health problem, about 2% of all children are hospitalised due to RSV bronchiolitis during their first 2 years of live. TLR4 has already been described in association with RSV associated diseases by us and others.Thus we were interested whether other TLRs are also involved in the genetics of severe RSV infection. We genotyped 19 polymorphisms in the autosomal TLRs, these are TLR1, 2, 3, 5, 6, 9 and 10. Association analyses by the Armitage's Trend test revealed weak association of one TLR9 promoter polymorphism with RSV infection (p= 0.013). In addition, association was found with TLR10 haplotypes (p= 0.024).We conclude from our data – that – although we can not rule out a minor involvement ofTLR9polymorphism andTLR10haplotypes – TLRs other than TLR4 do not play a major role in the genetics of severe RSV associated diseases. Future studies should focus on additional genes of the innate immune response.

Microbiota educates innate immune response to Toll-like receptors stimulation and RSV infection in lung

2019 ◽  
Author(s):  
Quentin Marquant ◽  
Daphné Laubreton ◽  
Carole Drajac ◽  
Elliot Mathieu ◽  
Marie-Louise Noordine ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Rsv Infection

scholarly journals TLR-4 andCD14 Polymorphisms in Respiratory Syncytial Virus Associated Disease

2006 ◽  
Vol 22 (5-6) ◽  
pp. 303-308 ◽  
Author(s):  
Beena Puthothu ◽  
Johannes Forster ◽  
Andrea Heinzmann ◽  
Marcus Krueger
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Amino Acid ◽  
Adaptive Immune Response ◽  
Host Cells ◽  
Respiratory Pathogen ◽  
Trend Test ◽  
Associated Diseases ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) is the most common viral respiratory pathogen during infancy world wide. It induces innate and adaptive immune response in host cells. The toll like receptor 4 (TLR4)/CD14 complex is particularly important for the initiation of an innate immune response to RSV. Thus we were interested whether an association exists between severe RSV associated diseases and polymorphisms within TLR4 and CD14.We genotyped the CD14 promotor polymorphism -C159T and the two common TLR4 amino acid variants (D259G, and T359I) in 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage’s trend test, haplotypes were calculated by FAMHAP, FASTEHPLUS and Arlequin.All polymorphisms were in Hardy Weinberg Equilibrium. We found marginal association between amino acid exchange D259G in TLR4 with RSV infectionp= 0.0545). Furthermore, haplotypes analysis of the two TLR4 polymorphisms by three independent programs revealed association of haplotypes with severe RSV infection (p≤ 0.0010). In contrast, the promotor polymorphism within CD14 was not associated with susceptibility to RSV disease. We conclude from our study, that TLR4 polymorphisms, and particularly the haplotypes, may influence the genetic predisposition to severe RSV infection.

scholarly journals Gene Expression Differences in Lungs of Mice during Secondary Immune Responses to Respiratory Syncytial Virus Infection

2010 ◽  
Vol 84 (18) ◽  
pp. 9584-9594 ◽  
Author(s):  
Annemieke Schuurhof ◽  
Louis Bont ◽  
Jeroen L. A. Pennings ◽  
Hennie M. Hodemaekers ◽  
Piet W. Wester ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Transcription Profiles ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Induced Immunity

ABSTRACT Vaccine-induced immunity has been shown to alter the course of a respiratory syncytial virus (RSV) infection both in murine models and in humans. To elucidate which mechanisms underlie the effect of vaccine-induced immunity on the course of RSV infection, transcription profiles in the lungs of RSV-infected mice were examined by microarray analysis. Three models were used: RSV reinfection as a model for natural immunity, RSV challenge after formalin-inactivated RSV vaccination as a model for vaccine-enhanced disease, and RSV challenge following vaccination with recombinant RSV virus lacking the G gene (ΔG-RSV) as a model for vaccine-induced immunity. Gene transcription profiles, histopathology, and viral loads were analyzed at 1, 2, and 5 days after RSV challenge. On the first 2 days after challenge, all mice displayed an expression pattern in the lung similar of that found in primary infection, showing a strong innate immune response. On day 5 after RSV reinfection or after challenge following ΔG-RSV vaccination, the innate immune response was waning. In contrast, in mice with vaccine-enhanced disease, the innate immune response 5 days after RSV challenge was still present even though viral replication was diminished. In addition, only in this group was Th2 gene expression induced. These findings support a hypothesis that vaccine-enhanced disease is mediated by prolonged innate immune responses and Th2 polarization in the absence of viral replication.

scholarly journals The Role of Alveolar Macrophages in the Improved Protection against Respiratory Syncytial Virus and Pneumococcal Superinfection Induced by the Peptidoglycan of Lactobacillus rhamnosus CRL1505

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1653 ◽  
Author(s):  
Patricia Clua ◽  
Mikado Tomokiyo ◽  
Fernanda Raya Tonetti ◽  
Md. Aminul Islam ◽  
Valeria García Castillo ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Innate Immune Response ◽  
Pneumococcal Pneumonia ◽  
Lactobacillus Rhamnosus ◽  
Innate Immune ◽  
Rsv Infection ◽  
Immunomodulatory Properties ◽  
Syncytial Virus

The nasal priming with nonviable Lactobacillus rhamnosus CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulates the respiratory innate immune response in infant mice, improving their resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, it was found that NV1505 or PG1505 significantly enhance the numbers of CD11c+SiglecF+ alveolar macrophages (AMs) producing interferon (IFN)-β. In this work, we aimed to further advance in the characterization of the beneficial effects of NV1505 and PG1505 in the context of a respiratory superinfection by evaluating whether their immunomodulatory properties are dependent on AM functions. Macrophage depletion experiments and a detailed study of their production of cytokines and antiviral factors clearly demonstrated the key role of this immune cell population in the improvement of both the reduction of pathogens loads and the protection against lung tissue damage induced by the immunobiotic CRL1505 strain. Studies at basal conditions during primary RSV or S. pneumoniae infections, as well as during secondary pneumococcal pneumonia, brought the following five notable findings regarding the immunomodulatory effects of NV1505 and PG1505: (a) AMs play a key role in the beneficial modulation of the respiratory innate immune response and protection against RSV infection, (b) AMs are necessary for improved protection against primary and secondary pneumococcal pneumonia, (c) the generation of activated/trained AMs would be essential for the enhanced protection against respiratory pathogens, (d) other immune and nonimmune cell populations in the respiratory tract may contribute to the protection against bacterial and viral infections, and (e) the immunomodulatory properties of NV1505 and PG1505 are strain-specific. These findings significantly improve our knowledge about the immunological mechanisms involved in the modulation of respiratory immunity induced by beneficial microbes.

scholarly journals Peptidomimetic 1-Benzyl-5-methyl-4-(n-octylamino)pyrimidin-2(1H)-one Showed Cardioprotection Effect in a Myocardial Ischemia (MI) Mouse Model

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 72
Author(s):  
Lena Trifonov ◽  
Vadim Nudelman ◽  
Michael Zhenin ◽  
Guy Cohen ◽  
Krzysztof Jozwiak ◽  
...  
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Myocardial Ischemia ◽  
Mouse Model ◽  
Innate Immune Response ◽  
Pattern Recognition Receptor ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Toll Like Receptors ◽  
Recognition Receptor

TLR4, a member of the toll-like receptors (TLRs) family, serves as a pattern recognition receptor in the innate immune response to different microbial pathogens. [...]

scholarly journals 2249

2017 ◽  
Vol 1 (S1) ◽  
pp. 59-59
Author(s):  
Darrell Dinwiddie ◽  
Walter Dehority ◽  
Kurt C. Schwalm ◽  
Raymond J. Langley ◽  
Stephen A. Young ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Pediatric Patients ◽  
Simultaneous Detection ◽  
Innate Immune ◽  
Host Gene ◽  
Mixed Cell ◽  
Significant Differential Expression ◽  
Rsv Infection

OBJECTIVES/SPECIFIC AIMS: Respiratory viruses cause enormous medical burden, yet many of the specific virus and host genetic factors that impact pathogenesis are still largely unknown or poorly understood. To better understand the drivers of both acute clinical pathogenesis and long-term impacts, such as the development of asthma, we investigated the host response to respiratory syncytial virus (RSV) infections in pediatric patients. METHODS/STUDY POPULATION: We collected nasopharyngeal swabs from 32 pediatric patients with acute RSV infection. The swabs represented a mixed cell population including epithelial and immune cells at the active site of infection. Unbiased RNA sequencing with ribosomal RNA depletion allowed the simultaneous detection of host gene expression and RSV infection. We sequenced samples 2×75 bp on an Illumina NextSeq 500. Sequences were mapped to the human genome using the TopHat 2 aligner and FPKM estimation of reference genes and transcripts and assembly of novel transcripts were conducted with Cufflinks 2. RESULTS/ANTICIPATED RESULTS: During acute RSV infection we identified 7343 genes that were significantly expressed. Pathway analysis using KEGG revealed significant upregulation of pathways involved in innate immune response infection, ribosome function, oxidative phosphorylation, spliceosome and autoimmune disorders. We found high levels of innate immune response genes including CXCL8, IFITM1, IFITM2, IFITM3, IL1RN, and ISG15. In comparing RSV subtype A to RSV B we found significant differential expression of multiple noncoding RNAs. DISCUSSION/SIGNIFICANCE OF IMPACT: Examination of the host gene response during acute RSV infections, yielded important insight into the mechanisms that cause clinical pathogenesis and may provide understanding of the mechanisms that lead to known long-term impacts, such as the development of asthma. Together, this data may be used to guide clinical treatment and management decisions for children with severe RSV infections.

scholarly journals Evidence for an Innate Immune Response in the Immature Human Intestine: Toll-Like Receptors on Fetal Enterocytes

2001 ◽  
Vol 49 (4) ◽  
pp. 589-593 ◽  
Author(s):  
Robert D Fusunyan ◽  
Nanda N Nanthakumar ◽  
Manuel E Baldeon ◽  
W Allan Walker
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Human Intestine ◽  
Toll Like Receptors

scholarly journals siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

Biomolecules ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 165 ◽  
Author(s):  
María Martín-Vicente ◽  
Salvador Resino ◽  
Isidoro Martínez
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Virus Replication ◽  
Innate Immune Response ◽  
Human Respiratory Syncytial Virus ◽  
Innate Immune ◽  
Viral Fusion ◽  
Small Interfering Rnas ◽  
Syncytial Virus ◽  
Nucleoprotein N

Human respiratory syncytial virus (HRSV) infection is a common cause of severe lower respiratory tract diseases such as bronchiolitis and pneumonia. Both virus replication and the associated inflammatory immune response are believed to be behind these pathologies. So far, no vaccine or effective treatment is available for this viral infection. With the aim of finding new strategies to counteract HRSV replication and modulate the immune response, specific small interfering RNAs (siRNAs) were generated targeting the mRNA coding for the viral fusion (F) protein or nucleoprotein (N), or for two proteins involved in intracellular immune signaling, which are named tripartite motif-containing protein 25 (TRIM25) and retinoic acid-inducible gene-I (RIG-I). Furthermore, two additional bispecific siRNAs were designed that silenced F and TRIM25 (TRIM25/HRSV-F) or N and RIG-I (RIG-I/HRSV-N) simultaneously. All siRNAs targeting N or F, but not those silencing TRIM25 or RIG-I alone, significantly reduced viral titers. However, while siRNAs targeting F inhibited only the expression of the F mRNA and protein, the siRNAs targeting N led to a general inhibition of viral mRNA and protein expression. The N-targeting siRNAs also induced a drastic decrease in the expression of genes of the innate immune response. These results show that both virus replication and the early innate immune response can be regulated by targeting distinct viral products with siRNAs, which may be related to the different role of each protein in the life cycle of the virus.

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