Different responses of murine and human macrophages to leptospiral infection revealed by comparative array analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE45170 | GEO | 2013/03/15
SECONDARY ACCESSION(S): PRJNA193098
REPOSITORIES: GEO
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Project description:Leptospirosis is a re-emerging tropical infectious disease caused by the pathogenic Leptospira spp. The different host innate immune responses were partially related to the different severity of leptospirosis. In this study, we employed transcriptomics and cytokine array to comparatively calculate the responses of murine peritoneal macrophages (MPM) and human peripheral blood monocytes (HBM) to leptospiral infection, and uncover a series of different expression regulations of these two immune cells. The regulation percentages in several biological processes of MPM, such as the antigen process and presentation, the regulation of membrane potential, and the innate immune response, etc., were much greater than those of HBM (>2 folds). In HBM and MPM, the CASP8 and FADD-like apoptosis regulator genes were significantly up-regulated, which supported previous results that the caspase-8/3 pathway plays an important role in macrophage apoptosis during leptospiral infection. The key component of complement pathway, C3, was only up-regulated in MPM. Several cytokines (e.g. IL-10, TNF-alpha) were differently expressed at both mRNA and protein level in MPM and HBM. The differences in the transcriptomics and the cytokine expression revealed in this study were partially consistent with the different outcomes of the chronic and acute leptospirosis; thus, these findings facilitated further molecular study on the innate immune response to leptospiral infection. Murine peritoneal macrophages (MPM) and human peripheral blood monocytes (HBM) were infected by pathogenic Leptospira. The host cells were collected at 1h, 2h, and 4h after infection. The uninfected macrophage sample was designed as a negative control. Three biological replicates were designed for each sample type. There were totally 24 hybridizations (12 for MPM, and 12 for HBM) included in this submission.
2013-03-15 | E-GEOD-45170 | biostudies-arrayexpress
Project description:Leptospirosis is a globally important infectious disease caused by an infection with pathogenic Leptospira spp. and associated with kidney injury due to sustained tubulointerstitial inflammation. We apply the high-throughput Illumina sequencing platforms to determine the murine renal transcriptome and investigate gene expression alterations and biological pathways associated with kidney damage induced by leptospiral infection. The goal of this study is to investigate a global analysis of renal gene expression associated with renal damage that was induced by leptospiral infection in experimental mice models.
2022-07-25 | GSE185382 | GEO
Project description:Leptospirosis is the most widespread zoonotic disease in the world. The lack of an adequate laboratory test is a major barrier for the diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response against leptospiral antigens from 274 individuals, including 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL and Loa22 are already known to be recognized by sera from human patients, thus serving as a proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the accuracy of these antigens in more appropriate diagnostic platforms. Antibody profiling was peformed on sera from infected and non-infected subjects to investigate the IgG response against leptospiral antigens. These samples comprised 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects, including 29 subjects from United States (non-endemic area), 35 blood donors from Salvador/Brazil (endemic area) and 50 healthy individuals from region with high endemicity of leptospirosis.
2012-12-04 | E-GEOD-42720 | biostudies-arrayexpress
Project description:Leptospirosis caused by pathogenic Leptospira spp. leads to kidney damage that may progress to chronic kidney disease. However, how leptospiral infections lead to renal damage is unclear. Here, we apply microarray platforms to determine the murine renal transcriptome-wide investigation of gene expression changes and biological pathways associated with leptospiral infection-related kidney damage. The aims of this study are to investigate a global analysis of renal gene expression associated with renal damage that was induced by leptospiral infection using experimental murine models. The result of microarray analysis showed that 467 and 927 genes to be differentially expressed in mice kidney with pathogenic leptospiral infection after day 7 and 28, respectively. Moreover, the result also showed that the 508 significantly differentially expressed genes in the kidneys of mice after infection with non-pathogenic leptospires at 7 days post-infection, and the 1,067 transcripts significantly differentially expressed in these kidneys at 28 days post-infection. Biological pathways performed using KEGG pathway enrichment analysis (P-value < 1E-5) showed that a total of 6 and 7 pathways were significantly enriched at 7 and 28 days post-infection with pathogenic leptospires, respectively. A total of 25 pathways were significantly enriched at day 28 following the non-pathogenic leptospiral infection. However, none of pathways were found in microarray data at day 7 post-infection with non-pathogenic leptospires. In addition, the antigen processing and presentation pathways was significantly enriched at 7 and 28 days post-infection with pathogenic leptospires, and at day 28 following the non-pathogenic leptospiral infection.
2021-02-23 | GSE111249 | GEO
Project description:Leptospirosis is the most widespread zoonotic disease in the world. The lack of an adequate laboratory test is a major barrier for the diagnosis, especially during the early stages of illness, when antibiotic therapy is most effective. Therefore, there is a critical need for an efficient diagnostic test for this life threatening disease. In order to identify new targets that could be used as diagnostic makers for leptopirosis, we constructed a protein microarray chip comprising 61% of Leptospira interrogans proteome and investigated the IgG response against leptospiral antigens from 274 individuals, including 80 acute-, 80 convalescent-phase patients and 114 healthy control subjects from regions with endemic, high endemic and no endemic transmission of leptospirosis. A nitrocellulose line blot assay was performed to validate the accuracy of the protein microarray results. We found 16 antigens that can discriminate between acute cases and healthy individuals from a region with high endemic transmission of leptospirosis, and 18 antigens that distinguish convalescent cases. Some of the antigens identified in this study, such as LipL32, the non-identical domains of the Lig proteins, GroEL and Loa22 are already known to be recognized by sera from human patients, thus serving as a proof-of-concept for the serodiagnostic antigen discovery approach. Several novel antigens were identified, including the hypothetical protein LIC10215 which showed good sensitivity and specificity rates for both acute- and convalescent-phase patients. Our study is the first large-scale evaluation of immunodominant antigens associated with naturally acquired leptospiral infection and novel as well as known serodiagnostic leptospiral antigens that are recognized by antibodies in the sera of leptospirosis cases were identified. The novel antigens identified here may have potential use in both the development of new tests and the improvement of currently available assays for diagnosing this neglected tropical disease. Further research is needed to assess the accuracy of these antigens in more appropriate diagnostic platforms.
2012-12-04 | GSE42720 | GEO
Project description:The biogenesis and functions of Leptospira's extracellular vesicles (EVs) remain unclear. The study aimed to characterize EVs that were naturally released from intact leptospires during in vitro culture, as well as under conditions mimicking the host environment during infection, including temperature or osmolarity shift. The EVs were found to contain a group of proteins from the outer membrane and various cytoplasmic proteins, suggesting that they originated from the outer membrane and cytoplasm. These proteins were primarily involved in Leptospira's growth, survival, adaptation, and pathogenicity. Interestingly, the study revealed that Leptospira secreted multifunctional proteins through EVs but might maintain several virulence and virulence-associated proteins in their cells in response to temperature and osmotic stresses. Thus, native leptospiral EVs might act as decoys for the host immune system, while the virulence factors crucial for direct interaction with host components might be preserved in whole cells. This knowledge may contribute to understanding the role of EVs in the pathogenicity of Leptospira and the development of vaccines against leptospirosis in the future.
2024-01-26 | PXD042648 | Pride
Project description:Leptospirosis is a zoonotic disease caused by Leptospira spp. that cause serious health burden. Humans are accidental host gets infected from water contaminated with Leptospira from urine of reservoir hosts like rodents and other mammals. Currently there is no effective vaccine available for leptospirosis. Investigations on post-translational modifications (PTMs) provide insights into the bacterial pathophysiology and functional consequences during bacterial infection and that can provide significant contribution in the search for better vaccine candidates. PTMs are decisive factors in the structure, function, and localization of proteins in both prokaryotic and eukaryotic organisms. In our previous investigations, we have identified PXD016204 (Thoduvayil et al., 2020) and PXD026044 (Sarma et al., 2021) from Leptospira interrogans serovar Copenhageni (strain Fiocruz L1-130). In this project, a systematic reanalysis of unassigned spectra were carried out from our previous total proteome data (PXD016204 and PXD026044) for multi-PTM analysis. We have identified a total of 3,693 unique high-confidence PTM sites corresponding to 1,266 proteins (PTM-Pro probability cut-off value is ≥75%). There were two objectives for the study. The first objective was the functional characterization of PTM proteins, through the identification of protein-protein interactions (PPI). This will enable us to understand the type and functions of PTMs. This analysis was supported by additional characteristics like gene ontology (GO), cluster of autologous groups (COG), other protein features and functions. The second objective was to find the relationship of PTMs with the subcellular localization of leptospiral proteins. We have analyzed the PTM containing proteins identified in Triton X-114 fractions and used the iBAQ values and number of PTM containing peptides that correlate with the sub-cellular localization of leptospiral proteins.
2022-08-12 | PXD030370 | Pride
Project description:Fibroblastic reticular cells (FRC) shape the organization of secondary lymphoid organs and actively promote the induction of immune responses by coordinating the interaction of innate and adaptive immune cells. However, the mechanisms underlying FRC functions during viral infections have remained largely unexplored. In the study, we combined FRC-specific genetic ablation of the type 1 IFN-alpha receptor (IFNAR) with high-dimensional transcriptomics analyses to elaborate the phenotypical alterations and functional consequences of impaired innate immunological sensing in FRC during lymph node-restricted viral infection
2020-09-01 | E-MTAB-8906 | biostudies-arrayexpress
Project description:Aguilera 2014 - HIV latency. Interaction
between HIV proteins and immune response
This model is described in the article:
Studying HIV latency by
modeling the interaction between HIV proteins and the innate
immune response.
Aguilera LU,
Rodríguez-González J.
J. Theor. Biol. 2014 Nov; 360:
67-77
Abstract:
HIV infection leads to two cell fates, the viral productive
state or viral latency (a reversible non-productive state). HIV
latency is relevant because infected active CD4+ T-lymphocytes
can reach a resting memory state in which the provirus remains
silent for long periods of time. Despite experimental and
theoretical efforts, the causal molecular mechanisms
responsible for HIV latency are only partially understood.
Studies have determined that HIV latency is influenced by the
innate immune response carried out by cell restriction factors
that inhibit the postintegration steps in the virus replication
cycle. In this study, we present a mathematical study that
combines deterministic and stochastic approaches to analyze the
interactions between HIV proteins and the innate immune
response. Using wide ranges of parameter values, we observed
the following: (1) a phenomenological description of the viral
productive and latent cell phenotypes is obtained by bistable
and bimodal dynamics, (2) biochemical noise reduces the
probability that an infected cell adopts the latent state, (3)
the effects of the innate immune response enhance the HIV
latency state, (4) the conditions of the cell before infection
affect the latent phenotype, i.e., the existing expression of
cell restriction factors propitiates HIV latency, and existing
expression of HIV proteins reduces HIV latency.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000573.
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.
2015-03-30 | BIOMD0000000573 | BioModels
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.
2014-04-03 | BIOMD0000000529 | BioModels