Dynamic changes of macrophage polarization during Salmonella infection in zebrafish
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE224985 | GEO | 2024/01/25
REPOSITORIES: GEO
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Project description:The immune response against pathogens involves multiple cell state transitions and complex gene expression changes. Here we established an in vivo single-cell nascent RNA labeling sequencing method (scnasRNA-seq) and applied it to survey time-resolved RNA dynamics during immune response to acute enteric infection with Salmonella. We showed that detection of nascent RNA synthesis reflects more realistic information on cell activation and gene transcription than total RNA level. Interplay of nascent RNA synthesis and RNA degradation together modulate dynamics of total RNA. We found that bone marrow macrophages are first primed at very early stage upon Salmonella infection. In contrast, the innate immune response of macrophages in intestine is limited. Notably, intestinal CD8+ T cells and plasma cells are rapidly and specifically activated at early stage post infection. Intestinal late enterocytes quickly express MHC-I molecules and present Salmonella antigen to CD8+ T cells for their activation, serving as antigen presenting cells for initiation of adaptive immunity. Our findings unveil novel RNA control strategies of immune cells and dynamic time course of immune response activation upon Salmonella infection, challenging the doctrine boundary between innate immunity and adaptive immunity against bacterial infection.
2024-10-17 | GSE279651 | GEO
Project description:The immune response against pathogens involves multiple cell state transitions and complex gene expression changes. Here we established an in vivo single-cell nascent RNA labeling sequencing method (scnasRNA-seq) and applied it to survey time-resolved RNA dynamics during immune response to acute enteric infection with Salmonella. We showed that detection of nascent RNA synthesis reflects more realistic information on cell activation and gene transcription than total RNA level. Interplay of nascent RNA synthesis and RNA degradation together modulate dynamics of total RNA. We found that bone marrow macrophages are first primed at very early stage upon Salmonella infection. In contrast, the innate immune response of macrophages in intestine is limited. Notably, intestinal CD8+ T cells and plasma cells are rapidly and specifically activated at early stage post infection. Intestinal late enterocytes quickly express MHC-I molecules and present Salmonella antigen to CD8+ T cells for their activation, serving as antigen presenting cells for initiation of adaptive immunity. Our findings unveil novel RNA control strategies of immune cells and dynamic time course of immune response activation upon Salmonella infection, challenging the doctrine boundary between innate immunity and adaptive immunity against bacterial infection.
2024-10-31 | GSE280764 | GEO
Project description:Salmonella must express and deploy a type III secretion system located in Salmonella pathogenicity island 2 (SPI-2) in order to survive in host phagocytic vacuoles and to cause systemic infection in mouse models of typhoid fever. A genome-wide approach to screening for Salmonella genes that are transcriptionally co-regulated in vitro with SPI-2 genes was used to identify bacterial loci that might function in a mouse model of systemic disease. Strains with mutations in three SPI-2 co-expressed genes were constructed and tested for their ability to cause disease in mice. We found that virK, a homologue of a Shigella virulence determinant, and rcsC, a sensor kinase, are important at late stages of infection. A second Salmonella gene that has VirK homology, somA, is also important for systemic infection in mice. We have shown that expression of both virK and somA requires the transcription factor PhoP, whereas rcsC does not. Additionally, rcsC expression does not require the transcription factor OmpR, but expression of one of the known targets of RcsC, the yojN rcsB putative operon, does require OmpR. virK, somA and rcsC are expressed in tissue culture macrophages and confer Salmonella resistance to the cationic peptide polymyxin B. We conclude that virK, somA and rcsC are important for late stages of Salmonella enteric fever, and that they probably contribute to the remodelling of the bacterial outer membrane in response to the host environment.
2005-10-07 | E-SMDB-1981 | biostudies-arrayexpress
Project description:Salmonella must express and deploy a type III secretion system located in Salmonella pathogenicity island 2 (SPI-2) in order to survive in host phagocytic vacuoles and to cause systemic infection in mouse models of typhoid fever. A genome-wide approach to screening for Salmonella genes that are transcriptionally co-regulated in vitro with SPI-2 genes was used to identify bacterial loci that might function in a mouse model of systemic disease. Strains with mutations in three SPI-2 co-expressed genes were constructed and tested for their ability to cause disease in mice. We found that virK, a homologue of a Shigella virulence determinant, and rcsC, a sensor kinase, are important at late stages of infection. A second Salmonella gene that has VirK homology, somA, is also important for systemic infection in mice. We have shown that expression of both virK and somA requires the transcription factor PhoP, whereas rcsC does not. Additionally, rcsC expression does not require the transcription factor OmpR, but expression of one of the known targets of RcsC, the yojN rcsB putative operon, does require OmpR. virK, somA and rcsC are expressed in tissue culture macrophages and confer Salmonella resistance to the cationic peptide polymyxin B. We conclude that virK, somA and rcsC are important for late stages of Salmonella enteric fever, and that they probably contribute to the remodelling of the bacterial outer membrane in response to the host environment. Groups of assays that are related as part of a time series. Computed
2005-12-02 | E-GEOD-3735 | biostudies-arrayexpress
Project description:Salmonella must express and deploy a type III secretion system located in Salmonella pathogenicity island 2 (SPI-2) in order to survive in host phagocytic vacuoles and to cause systemic infection in mouse models of typhoid fever. A genome-wide approach to screening for Salmonella genes that are transcriptionally co-regulated in vitro with SPI-2 genes was used to identify bacterial loci that might function in a mouse model of systemic disease. Strains with mutations in three SPI-2 co-expressed genes were constructed and tested for their ability to cause disease in mice. We found that virK, a homologue of a Shigella virulence determinant, and rcsC, a sensor kinase, are important at late stages of infection. A second Salmonella gene that has VirK homology, somA, is also important for systemic infection in mice. We have shown that expression of both virK and somA requires the transcription factor PhoP, whereas rcsC does not. Additionally, rcsC expression does not require the transcription factor OmpR, but expression of one of the known targets of RcsC, the yojN rcsB putative operon, does require OmpR. virK, somA and rcsC are expressed in tissue culture macrophages and confer Salmonella resistance to the cationic peptide polymyxin B. We conclude that virK, somA and rcsC are important for late stages of Salmonella enteric fever, and that they probably contribute to the remodelling of the bacterial outer membrane in response to the host environment. Groups of assays that are related as part of a time series. Keywords: time_series_design
2005-12-03 | GSE3735 | GEO
Project description:Potato (Solanum tuberosum) late blight disease caused by Phytophthora. infestans is one of the most critical crop diseases in the world. We investigated the proteome of Solanum tubersoum (cv. Sarpo Mira) by quantitative proteomics after foliar application of encysted zoospore suspension from P. infestans isolate. Also, we examined changes in protein abundance of cv. Sarpo Mira in response to P. infestans infection at three key timepoints 0 hpi (L), 48 hpi (M) and 120 hpi (H), divided into early and late disease stages and analyzed the protein-protein interaction during the disease stages. In response to P. infestans oomycete infection, the iTRAQ comparative proteome survey revealed a total of 1229 differentially expressed proteins (DEPs) in the pairwise comparison of disease stages, which included DEPs specific to early disease stage, DEPs specific to late disease stage and commonly shared DEPs. Over 80% of the change in protein abundance were up-regulated in the early stages of infection while about 61% of the DEPs in the later disease stage were down-regulated. The analysis of expression patterns, functional category, and enrichment tests highlighted significant coordination and enrichment of cell wall-associated defense response proteins in the early stages and cellular protein modification process as well as membrane protein complex formation in the late stages. Furthermore, strong protein interactions were observed in the late disease stage that might relate to disease pathogenesis.
2019-01-09 | PXD010045 | Pride
Project description:Salmonella is an intracellular pathogen causing significant morbidity and mortality. Its ability to grow inside macrophages is important to virulence, and is dependent on the activation state of the macrophages. Classically activated M1 macrophages are non-permissive for Salmonella growth, while alternatively activated M2 macrophages are permissive for Salmonella growth. Here we showed that endotoxin-primed macrophages (MEP), such as those associated with sepsis, showed similar levels of Salmonella resistance to M1 macrophages after 2 hr of intracellular infection, but at the 4 hr and 24 hr time points were susceptible like M2 macrophages. To understand this mechanistically, transcriptome sequencing, RNA-Seq, was performed. This showed that M1 and MEP macrophages that had not been exposed to Salmonella, demonstrated a process termed here as primed activation, in expressing relatively higher levels of particular anti-infective genes and pathways, including the JAK-STAT pathway. In contrast, in M2 macrophages these genes and pathways were largely expressed only in response to infection. Conversely, in response to infection, M1 macrophages, but not MEP macrophages, modulated additional genes known to be associated with susceptibility to Salmonella infection, possibly contributing to the differences in resistance at later time points. Application of the JAK inhibitor Ruxolitinib before infection reduced resistance in M1 macrophages, supporting the importance of early JAK-STAT signalling in M1 resistance to Salmonella.
2022-10-03 | GSE189847 | GEO
Project description:To investigate the extent to which macrophages respond to Salmonella infection, researchers infected RAW 264.7 macrophages with Salmonella enterica serotype Typhimurium and analyzed macrophage proteins at various time points following infection by using a global proteomic approach.
2013-10-07 | PXD000389 | Pride
Project description:We used Arabidopsis full-genome microarrays to characterize plant transcript accumulations at different stages of infection with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis : initiation (< 1 dpi) and maintenance of infection (> 4 dpi). In two independent experiments, cotyledons from the ecotype Wassilewskija (WS) were inoculated with water, or with Hyaloperonospora arabidopsidis to establish a compatible interaction. Affymetrix ATH1 microarrays were used to profile Arabidopsis transcript accumulations at the initiation (mixed samples at 8 and 24 hours post inoculation, hpi; early stage) and maintenance (mixed samples at 4 and 6 days post inoculation; late stage) of the compatible interaction.
2010-04-07 | E-GEOD-21076 | biostudies-arrayexpress
Project description:We employed microarray expression profiling to identify genes which are differentially regulated in the absence of FoxO3a, upon Salmonella typhimurium (ST) infection. ST induced gene expression changes were measured in Wild-type and FoxO3a-/- bone marrow derived macroophages at 6 hours post infection. The array showed an enrichment of MAPK signaling and alterations in inflammatory cytokines and ROS regulators in the absence of FoxO3a. Gene expression changes in bone marrow derived macrophages was measured after infection with 10 MOI of Salmonella typhimurium. Control samples were left untreated. Two mice from each genotype were used for the experiment.
2016-08-11 | GSE82212 | GEO