Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Jäger, Elisabeth; Schulz, Angela; Lede, Vera; Chen, Lin; Schöneberg, Torsten; Duc, Diana Le

doi:10.4049/jimmunol.1501326

Cited by 18 publications

(12 citation statements)

References 46 publications

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“…RIG-I is a pattern recognition receptor involved in viral RNA recognition, critical for the host antiviral response. The top downregulated genes included Rtn4rl1 ; the apoptosis activator Bmg ; the receptor Epha2 , whose absence is associated with a reduced bacterial load during the chronic phase of M. tuberculosis infection in mice 28 ; Gpr34, whose deficiency in mice has been associated with an altered immune response 29 30 ; the chemokine Ccl24 ; and the scavenger receptor Fcrls .…”

Section: Resultsmentioning

confidence: 99%

Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis

Andreu

Phelan

Sessions

et al. 2017

Sci Rep

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Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M. tuberculosis. We show that infection with live bacilli specifically alters the expression of host genes such as Rsad2, Ifit1/2/3 and Rig-I, whose potential roles in resistance to M. tuberculosis infection have not yet been investigated. In addition, the response of primary macrophages is faster and more intense than that of J774 cells in terms of number of differentially expressed genes and magnitude of induction/repression. Our results point to potentially novel processes leading to immune containment early during M. tuberculosis infection, and support the idea that important differences exist between primary macrophages and cell lines, which should be taken into account when choosing a macrophage model to study host-pathogen interactions.

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Section: Resultsmentioning

confidence: 99%

Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis

Andreu

Phelan

Sessions

et al. 2017

Sci Rep

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“…Several IFNinducible GTPases (GBPs), including GBP1, GBP4, and GBP5, IFN-stimulated genes (ISGs), such as ISG20, RSAD2, and IRF1 (interferon-regulatory factors 1), and pro-apoptotic genes (PTGS2) were also induced. Only two genes (PDK4 and GPR34) with a deficiency in mice were associated with an altered immune response in TB (49,50) and downregulated. To obtain more information on the functional organization of the genes, they were subjected to functional enrichment and network interaction analysis (Figure 2).…”

Section: Transcriptomic Response Of Amcts and Amtbs To Infection Withmentioning

confidence: 99%

Human Alveolar and Splenic Macrophage Populations Display a Distinct Transcriptomic Response to Infection With Mycobacterium tuberculosis

2020

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Mycobacterium tuberculosis (Mtb) infects alveolar macrophages (AMs), causing pulmonary tuberculosis (PTB), the most common form of the disease. Less frequently, Mtb is disseminated to many other organs and tissues, resulting in different extrapulmonary forms of TB. Nevertheless, very few studies have addressed the global mRNA response of human AMs, particularly from humans with the active form of the disease. Strikingly, almost no studies have addressed the response of human extrapulmonary macrophages to Mtb infection. In this pilot study, using microarray technology, we examined the transcriptomic ex vivo response of AMs from PTB patients (AMTBs) and AMs from control subjects (AMCTs) infected with two clinical isolates of Mtb. Furthermore, we also studied the infection response of human splenic macrophages (SMs) to Mtb isolates, as a model for extrapulmonary infection, and compared the transcriptomic response between AMs and SMs. Our results showed a striking difference in global mRNA profiles in response to infection between AMs and SMs, implicating a tissue-specific macrophage response to Mtb.

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“…To identify molecular pathways that may be affected by the gene expression profiles we performed GO enrichment analysis followed by protein-protein-interaction (PPI) networks, as previously described 37,38 . Using the mouse data, we identified general GO categories like cellular components or developmental processes to be enriched with DEGs (Supplementary Table S2).…”

Section: Resultsmentioning

confidence: 99%

Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion

Körner

Velluva

Bundalian

et al. 2022

Preprint

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Background: The 15q13.3 microdeletion has pleiotropic effects ranging from apparently healthy to severely affected individuals. The underlying basis of the variable phenotype remains elusive. Methods: We analyzed gene expression using blood from 3 individuals with 15q13.3 microdeletion and brain cortex tissue from 10 mice Df[h15q13]/+. We assessed differentially expressed genes (DEGs), protein-protein interaction (PPI) functional modules, and gene expression in brain developmental stages. Results: The deleted genes' haploinsufficiency was not transcriptionally compensated, suggesting a dosage effect may contribute to the pathomechanism. DEGs shared between tested individuals and a corresponding mouse model show a significant overlap including genes involved in monogenic neurodevelopmental disorders. Yet, network-wide dysregulatory effects suggest the phenotype is not caused by a singular critical gene. A significant proportion of blood DEGs, silenced in adult brain, have maximum expression during the prenatal brain development. Based on DEGs and their PPI partners we identified altered functional modules related to developmental processes, including nervous system development. Conclusions: We show that the 15q13.3 microdeletion has a ubiquitous impact on the transcriptome pattern, especially dysregulation of genes involved in brain development. The high phenotypic variability seen in 15q13.3 microdeletion could stem from an increased vulnerability during brain development, instead of a specific pathomechanism.

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Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Cited by 18 publications

References 46 publications

Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis

Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis

Human Alveolar and Splenic Macrophage Populations Display a Distinct Transcriptomic Response to Infection With Mycobacterium tuberculosis

Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion

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