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.

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 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.

Pattern of Ly49A Receptor Downregulation in Low-Level Prenatal Allogeneic Chimeras Suggests Threshold of Chimerism Needed for Long-Term Engraftment.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1201-1201
Author(s):  
Aimen F. Shaaban ◽  
Deepika Rajesh ◽  
Alan W. Flake
Keyword(s):  
Immune Response ◽  
Nk Cells ◽  
Innate Immune Response ◽  
Peripheral Blood ◽  
Pearson Correlation ◽  
Innate Immune ◽  
Receptor Expression ◽  
Hematopoietic Stem ◽  
Low Levels

Abstract Despite clinical success with in utero hematopoietic stem cell transplantation in immunodeficient recipients, only microchimerism (<0.1%) has been observed in immunocompetent human or non-human primate hosts without conditioning. It has been postulated that an innate immune response to the low levels of chimerism caused the lack of engraftment. We have found that prenatal murine recipients of fetal allografts with low levels of engraftment (<2.0%) also lose their chimerism after a few months. To better understand fetal innate immunity as it relates to this problem, we studied the education of host NK cells in prenatal chimeras with low engraftment (<5.0%). We hypothesized that alloreactive NK receptor expression correlates with chimerism level. To test this hypothesis, prenatal chimeras were created by transplanting fetal liver light density cells from 14 dpc Balb/c (H2d) fetuses into 14 dpc B6 (H2b) fetuses by IP injection. Using flow cytometry, peripheral blood chimerism in the pups was first assessed at 3 weeks and followed for one year. At 12 weeks, following the acquisition of mature NK inhibitory receptors, the level of H-2d alloreactive Ly49A, C, F, G, and I receptor expression among host splenic NK cells was measured. The mean fluorescence intensity for each receptor relative to age-matched controls (rMFI) was plotted against chimerism and the Pearson correlation coefficient (r) calculated for comparison. Chimerism ranged from 0.1 – 5.0% without GVHD (n=13). As shown in figure 1, B6 recipient NK cells exhibited a dramatic negative correlation of Ly49A expression with increasing chimerism (rMFI = 38 –118%, r = −0.87) without change in the frequency of Ly49A+ NK cells (18–26%, r=0.37). No significant change in the expression of Ly49C, F, G, or I was seen within the range of chimerism analyzed. Five mice reached 12 months and were sacrificed for a repeat NK analysis to determine the stability of Ly49A expression, see table 1. In four mice, chimerism and Ly49A expression levels did not change significantly. However, chimerism was lost in one animal with a corresponding upregulation in Ly49A expression. The initial chimerism level was in a range where we find that very few mice maintain long-term chimerism in this system (<2.0%). The pattern of progressive Ly49A downregulation with increasing peripheral blood chimerism strongly supports a mechanism of NK education that is developmentally responsive to the composite MHC expression in the host chimera. This suggests that a threshold level of chimerism may be necessary to overcome the host innate immune response. Possible mechanisms by which this may occur include higher levels chimerism leading to further NK inhibition or possibly the expansion of a critical regulatory cell population in the donor cell fraction. An understanding of these potential mechanisms will facilitate the development of more effective transplantation regimens. Table 1. Expression of Ly49A at 3 months and 1 year Chimerism Level Ly49A expression Animal PB-3 months (%) PB-12 months (%) rMFI-3 months (%) rMFI-12 months (%) 7831 0.2 0.1 76 74 7759* 1.33 0.2 38 92 7830 3.22 1.81 45 29 7860 1.91 2.38 42 33 7838 4.9 5.2 38 32

scholarly journals Is It Possible To Induce The "Spontaneous Regression" Of Cancer? A Mechanism of Activation for the Innate Immune Response

2016 ◽  
Vol 2 (1) ◽  
Author(s):  
Jozef Oleksyszyn
Keyword(s):  
Immune Response ◽  
Lactic Acid ◽  
Innate Immune Response ◽  
Immune Cells ◽  
Spontaneous Regression ◽  
Atp Synthesis ◽  
Innate Immune ◽  
High Level ◽  
Cancerous Cells

The article deals with a theoretical model  of the mechanism of the spontaneous regression of tumor, involving the activation of innate immune response. After stimulation the cells of the immune system, use glycolysis for ATP synthesis.  Lactic acid, the final product of glycolysis, acts as inhibitor of such activation. Therefore, highly glycolytic cancerous cells form the environment (hypoglycemia with high level of lactic acid), which is strongly inhibitory to immune cells activation. Starvation, KD (ketogenic diet) and Coley’s toxin induce hypoglycemia and in the long term should also lower lactic acid level. After a few days of such treatment the glucose level could increase naturally due to gluconeogenesis or by the application of significant dose of glucose. Such procedure should induce activation of immune cells response (high glucose and low lactic acid levels) and a spontaneous regression of cancer. If lactic acid concentration remained still too high and thus inhibit the activation of immune cells, the organism would require alkalization because sodium lactate is not inhibitory  to the activation of immune cells. The model explains the cases of spontaneous regression described in literature and could be easily verified  experimentally.

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.

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