Single-cell transcriptome of human epithelial cells reveals novel insights into early innate immune responses to influenza virus and viral antagonism
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE122031 | GEO | 2019/07/08
REPOSITORIES: GEO
Similar Datasets
Project description:Fribourg2014 - Dynamics of viral antagonism and innate immune response (H1N1 influenza A virus - NC/99)
The dynamics of the interplay between the viral antagonism and the innate immune response has been studied using modelling approaches. The responses of human monocyte-derived dendritic cells infected by two influenza A H1N1 strains (the pandemic swine-origin A/California/4/2009 (Cal/09) and the seasonal A/New Caledonia/20/1999 (NC/99)) that have different clinical outcomes have been modelled. From the time course gene expression measurements of a set of selected genes, the dynamic features of viral antagonism and innate immune response are extracted. It is found that the strength and the time scale of action of viral antagonism is significantly different between the two viruses. This model describes the viral infection by seasonal NC/99.
This model is described in the article:
Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response.
Fribourg M, Hartmann B, Schmolke M, Marjanovic N, Albrecht RA, García-Sastre A, Sealfon SC, Jayaprakash C, Hayot F.
J Theor Biol. 2014 Mar 2;351C:47-57.
Abstract:
Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.
This model is hosted on BioModels Database and identified
by: MODEL1403310001.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication for more information.
2024-09-02 | BIOMD0000000529 | BioModels
Project description:Fribourg2014 - Dynamics of viral antagonism and innate immune response (H1N1 influenza A virus - Cal/09)
The dynamics of the interplay between the viral antagonism and the innate immune response has been studied using modelling approaches. The responses of human monocyte-derived dendritic cells infected by two influenza A H1N1 strains (the pandemic swine-origin A/California/4/2009 (Cal/09) and the seasonal A/New Caledonia/20/1999 (NC/99)) that have different clinical outcomes have been modelled. From the time course gene expression measurements of a set of selected genes, the dynamic features of viral antagonism and innate immune response are extracted. It is found that the strength and the time scale of action of viral antagonism is significantly different between the two viruses. This model describes the viral infection by seasonal Cal/09.
This model is described in the article:
Model of influenza A virus infection: Dynamics of viral antagonism and innate immune response.
Fribourg M, Hartmann B, Schmolke M, Marjanovic N, Albrecht RA, García-Sastre A, Sealfon SC, Jayaprakash C, Hayot F.
J Theor Biol. 2014 Mar 2;351C:47-57.
Abstract:
Viral antagonism of host responses is an essential component of virus pathogenicity. The study of the interplay between immune response and viral antagonism is challenging due to the involvement of many processes acting at multiple time scales. Here we develop an ordinary differential equation model to investigate the early, experimentally measured, responses of human monocyte-derived dendritic cells to infection by two H1N1 influenza A viruses of different clinical outcomes: pandemic A/California/4/2009 and seasonal A/New Caledonia/20/1999. Our results reveal how the strength of virus antagonism, and the time scale over which it acts to thwart the innate immune response, differs significantly between the two viruses, as is made clear by their impact on the temporal behavior of a number of measured genes. The model thus sheds light on the mechanisms that underlie the variability of innate immune responses to different H1N1 viruses.
This model is hosted on BioModels Database and identified
by: MODEL1403310002.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication for more information.
2024-09-02 | BIOMD0000000528 | BioModels
Project description:A. Esteban Hernandez-Vargas & Michael Meyer-Hermann. Innate Immune System Dynamics to Influenza Virus. IFAC Proceedings Volumes 45, 18 (2012).
The understanding of how influenza virus infection activates the immune system is crucial to designing prophylactic and therapeutic strategies against the infection. Nevertheless, the immune response to influenza virus infection is complex and remains largely unknown. In this paper we focus in the innate immune response to influenza virus using a mathematical model, based on interferon-induced resistance to infection of respiratory epithelial cells and the clearance of infected cells by natural killers. Simulation results show the importance of IFN-I to prevent new infections in epithelial cells and to stop the viral explosion during the first two days after infection. Nevertheless, natural killers response might be the most relevant for the first depletion in viral load due to the elimination of infected cells. Based on the reproductive number, the innate immune response is important to control the infection, although it would not be enough to clear completely the virus. The effective coordination between innate and adaptive immune response is essential for the virus eradication.
2024-09-02 | BIOMD0000000710 | BioModels
Project description:A. Esteban Hernandez-Vargas & Michael Meyer-Hermann. Innate Immune System Dynamics to Influenza Virus. IFAC Proceedings Volumes 45, 18 (2012).
The understanding of how influenza virus infection activates the immune system is crucial to designing prophylactic and therapeutic strategies against the infection. Nevertheless, the immune response to influenza virus infection is complex and remains largely unknown. In this paper we focus in the innate immune response to influenza virus using a mathematical model, based on interferon-induced resistance to infection of respiratory epithelial cells and the clearance of infected cells by natural killers. Simulation results show the importance of IFN-I to prevent new infections in epithelial cells and to stop the viral explosion during the first two days after infection. Nevertheless, natural killers response might be the most relevant for the first depletion in viral load due to the elimination of infected cells. Based on the reproductive number, the innate immune response is important to control the infection, although it would not be enough to clear completely the virus. The effective coordination between innate and adaptive immune response is essential for the virus eradication.
2024-09-02 | BIOMD0000000710 | BioModels
Project description:The influenza virus is a major cause of morbidity and mortality worldwide, yet, the impact of intracellular viral invasion and the cellular response diversity remain uncharacterized. By massively parallel single-cell RNA-seq we comprehensively mapped the host lung response to in-vivo influenza infection in wild-type and Irf7-knockout mice across nine immune and non-immune cell types. We found an unexpected high prevalence of infected cells in all cell types, showed that infection is a characteristic property of cell types that is independent of type-I interferon activity, and demonstrated that all cell types responded primarily with a robust generic transcriptional response. Analysis of the viral and host transcriptomes in the same single cell enabled us to resolve the heterogeneity of bystander (exposed but uninfected) as compared to viral-infected cells. Our results highlight novel markers specific for influenza-infected as opposed to bystander cells, opening new avenues for targeted therapy aimed exclusively at infected cells.
2018-06-06 | GSE107947 | GEO
Project description:Baris Hancioglu, David Swigon & Gilles Clermont. A dynamical model of human immune response to influenza A virus infection. Journal of Theoretical Biology 246, 1 (2007).
We present a simplified dynamical model of immune response to uncomplicated influenza A virus (IAV) infection, which focuses on the control of the infection by the innate and adaptive immunity. Innate immunity is represented by interferon-induced resistance to infection of respiratory epithelial cells and by removal of infected cells by effector cells (cytotoxic T-cells and natural killer cells). Adaptive immunity is represented by virus-specific antibodies. Similar in spirit to the recent model of Bocharov and Romanyukha [1994. Mathematical model of antiviral immune response. III. Influenza A virus infection. J. Theor. Biol. 167, 323-360], the model is constructed as a system of 10 ordinary differential equations with 27 parameters characterizing the rates of various processes contributing to the course of disease. The parameters are derived from published experimental data or estimated so as to reproduce available data about the time course of IAV infection in a naïve host. We explore the effect of initial viral load on the severity and duration of the disease, construct a phase diagram that sheds insight into the dynamics of the disease, and perform sensitivity analysis on the model parameters to explore which ones influence the most the onset, duration and severity of infection. To account for the variability and speed of adaptation of the adaptive response to a particular virus strain, we introduce a variable that quantifies the antigenic compatibility between the virus and the antibodies currently produced by the organism. We find that for small initial viral load the disease progresses through an asymptomatic course, for intermediate value it takes a typical course with constant duration and severity of infection but variable onset, and for large initial viral load the disease becomes severe. This behavior is robust to a wide range of parameter values. The absence of antibody response leads to recurrence of disease and appearance of a chronic state with nontrivial constant viral load.
2024-09-02 | BIOMD0000000711 | BioModels
Project description:Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection have the potential to limit virus replication and induce effective adaptive immune responses. However, relatively little is known about the importance of this innate anti-viral response to infection. Avian influenza viruses are a potential source of future pandemics, therefore it is critical to examine the effectiveness of the host anti-viral system to different influenza viruses. We used a human influenza (H3N2) and a low pathogenic avian influenza (H11N9) to assess and compare the anti-viral responses of bronchial epithelial cells (BECs). After infection, the H3N2 virus replicated more effectively than the H11N9 strain in BECs. This was not due to differential expression of different sialic acid residues on BECs but was attributed to the interference of the host anti-viral responses by H3N2. The H3N2 strain induced a delay in anti-viral signaling and impaired release of type I and type III interferons (IFNs) compared to the H11N9 virus. We then transfected the gene encoding for non-structural (NS) 1 protein into the BECs and the H3N2 NS1 induced a greater inhibition of anti-viral responses compared to the H11N9 NS1. While the low pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs and this may be at least in part due to a differential ability of the two NS1 proteins to inhibit anti-viral responses. This suggests that the subversion of human anti-viral responses may be an important requirement for influenza viruses to adapt to the human host and induce disease.
2009-12-19 | GSE19580 | GEO
Project description:Miao2010 - Innate and adaptive immune
responses to primary Influenza A Virus infection
This model is described in the article:
Quantifying the early immune
response and adaptive immune response kinetics in mice infected
with influenza A virus.
Miao H, Hollenbaugh JA, Zand MS,
Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ.
J. Virol. 2010 Jul; 84(13):
6687-6698
Abstract:
Seasonal and pandemic influenza A virus (IAV) continues to
be a public health threat. However, we lack a detailed and
quantitative understanding of the immune response kinetics to
IAV infection and which biological parameters most strongly
influence infection outcomes. To address these issues, we use
modeling approaches combined with experimental data to
quantitatively investigate the innate and adaptive immune
responses to primary IAV infection. Mathematical models were
developed to describe the dynamic interactions between target
(epithelial) cells, influenza virus, cytotoxic T lymphocytes
(CTLs), and virus-specific IgG and IgM. IAV and immune kinetic
parameters were estimated by fitting models to a large data set
obtained from primary H3N2 IAV infection of 340 mice. Prior to
a detectable virus-specific immune response (before day 5), the
estimated half-life of infected epithelial cells is
approximately 1.2 days, and the half-life of free infectious
IAV is approximately 4 h. During the adaptive immune response
(after day 5), the average half-life of infected epithelial
cells is approximately 0.5 days, and the average half-life of
free infectious virus is approximately 1.8 min. During the
adaptive phase, model fitting confirms that CD8(+) CTLs are
crucial for limiting infected cells, while virus-specific IgM
regulates free IAV levels. This may imply that CD4 T cells and
class-switched IgG antibodies are more relevant for generating
IAV-specific memory and preventing future infection via a more
rapid secondary immune response. Also, simulation studies were
performed to understand the relative contributions of
biological parameters to IAV clearance. This study provides a
basis to better understand and predict influenza virus
immunity.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000546.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000546 | BioModels
Project description:Respiratory viral infections contribute substantially to global infant losses and disproportionately affect preterm neonates. Using our previously established neonatal murine model of influenza infection, we demonstrate that three-day old mice are exceptionally sensitive to influenza virus infection and exhibit high mortality and viral load. Intranasal pre- and post-treatment of neonatal mice with Lactobacillus rhamnosus GG (LGG), an immune modulator in respiratory viral infection of adult mice and human preterm neonates, considerably improves neonatal mice survival after influenza virus infection. We determine that both live and heat-killed intranasal LGG are equally efficacious in protection of neonates. Early in influenza infection, neonatal transcriptional responses in the lung are delayed compared to adults. These responses increase by 24 hours post-infection, demonstrating a delay in the kinetics of the neonatal anti-viral response. LGG pretreatment improves immune gene transcriptional responses during early infection and specifically upregulates type I IFN pathways.
2019-09-18 | GSE137615 | GEO
Project description:The goal of this experiment was to examine the innate immune response to helminth infection in the lung. Hookworms (like many other helminths) use an obligate migration pathway through the lung. Their infection has been characterized in the gut in detail, but early immune responses in the lung have not been fully characterized. Experiment Overall Design: SCID mice were used to examine the innate immune response. SCID mice have no functional B or T cells but a fully functional innate immune system. SCID and WT mice were infected with 500 L3 stage infectious Nippostrongylus brasiliensis SC and their lungs were removed at days 2,3,4,8 and 12 post infection.
2007-12-01 | E-GEOD-3414 | biostudies-arrayexpress