Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria

ABSTRACT: Tumor Progression Locus 2 (TPL-2) kinase mediates Toll-like Receptor (TLR) activation of ERK1/2 and p38 MAP kinases in myeloid cells to modulate expression of key cytokines in innate immunity. This study identified a novel MAP kinase-independent regulatory function for TPL-2 in phagosome maturation, an essential process for killing of phagocytosed microbes. TPL-2 catalytic activity was demonstrated to induce phagosome acidification and proteolysis in primary mouse and human macrophages following uptake of latex beads. Quantitative proteomics revealed that blocking TPL-2 catalytic activity significantly altered the protein composition of phagosomes, particularly reducing the abundance of V-ATPase proton pump subunits. Furthermore, TPL-2 stimulated the phosphorylation of DMXL1, a critical regulator of V-ATPases, to induce phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome maturation and the efficient killing of Staphylococcus aureus following phagocytic uptake by macrophages. These results indicate that TPL-2 controls the innate immune response of macrophages to bacteria via V-ATPase induction of phagosome maturation.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow, Macrophage

SUBMITTER: Helen Flynn

LAB HEAD: Bram Snijders

PROVIDER: PXD020247 | Pride | 2021-03-24

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	ICL9283A25RW21_A1.raw	Raw
	ICL9283A25RW22_A1.raw	Raw
	ICL9283A25RW23_A2.raw	Raw
	ICL9283A25RW24_A2.raw	Raw
	ICL9283A25RW25_A3.raw	Raw

Items per page:

1 - 5 of 37

Similar Datasets

TPL-2 kinase induces phagosome acidification to promote macrophage killing of Staphylococcus aureus

Project description:Tumor Progression Locus 2 (TPL-2) kinase mediates Toll-like Receptor (TLR) activation of ERK1/2 and p38-alpha MAP kinases in myeloid cells to modulate expression of key cytokines in innate immunity. This study identified a novel MAP kinase-independent regulatory function for TPL-2 in phagosome maturation, an essential process for killing of phagocytosed bacteria. TPL-2 catalytic activity was demonstrated to induce phagosome acidification and proteolysis in primary mouse and human macrophages following uptake of latex beads. Mass spectrometry analysis revealed that blocking TPL-2 catalytic activity significantly altered the protein composition of phagosomes, particularly reducing the abundance of V-ATPase proton pump subunits. Furthermore, TPL-2 was shown to stimulate the phosphorylation of DMXL1, a critical regulator of V-ATPases, to induce phagosome acidification. Consistent with these results, TPL-2 catalytic activity was required for phagosome acidification, activation of phagosome acid-sensitive cathepsins and the efficient killing of Staphylococcus aureus following phagocytic uptake by macrophages. These results indicate that TPL-2 controls the innate immune response of macrophages to bacteria via MAP kinase regulation of gene expression and V-ATPase induction of phagosome maturation.

2021-02-11 | PXD020401 | Pride

LRRK2 signalling pathway in Mycobacterium tuberculosis

Project description:LRRK2 promotes Mycobacterium tuberculosis clearance by regulating phagosome maturation in mouse macrophages

2018-05-16 | PXD006909 | Pride

Mycobacterium avium subsp. paratuberculosis (MAP) during bovine monocyte-derived macrophage infection: untreated vs. bafilomcyin A1 treatment

Project description:Transcriptional profiling of M. avium subsp. paratuberculosis inside bovine monocyte-derived macrophages (MDMs; in vitro infection) during phagosome acidification at 30 min post-infection. M. avium subsp. paratuberculosis profiles from bafilomcyin A1 (acidification inhibitor) treated and untreated monocyte-derived macrophages were compared. Two-condition experiment; 3 control (bafilomcyin treated) and 3 test, independently conducted. 1 control, 1 test per microarray.

2016-07-29 | E-GEOD-84708 | biostudies-arrayexpress

Expression analysis of Mycobacterium avium subsp. paratuberculosis K-10 within macrophage cell line

2013-01-22 | GSE43645 | GEO

Mycobacterium avium subsp. paratuberculosis (MAP) during bovine monocyte-derived macrophage infection: untreated vs. bafilomcyin A1 treatment

2016-07-29 | GSE84708 | GEO

Expression analysis of Mycobacterium avium subsp. paratuberculosis K-10 within macrophage cell line

Project description:Once entering the cell, M. avium subsp.paratuberculosis is known to survive harsh microenvironments, especially those inside activated macrophages. To improve our understanding of M. avium subsp.paratuberculosis pathogenesis, we examined the phagosome maturation associated with transcriptional responses of M. avium subsp.paratuberculosis during macrophage infection. Monitoring cellular markers, only live M. avium subsp.paratuberculosis bacilli were able to prevent phagosome maturation and reduce its acidification. On the transcriptional level, over 300 of M. avium subsp.paratuberculosis genes were significantly, differentially regulated in both naM-CM-/ve and IFN-M-NM-3-activated macrophages. These genes include the sigma factor H (sigH) that was shown to be important during persistent infection in M. tuberculosis. Bacterial total RNA was purified from Mycobacterium avium subsp. paratuberculosis that was infected into J774A.1 cells grown with or without interferon-gamma activation at 2 or 24 h post-infection. RNA from bacteria incubated with PRMI-1640 medium for 2 h, which was the infection conditon, is used as control condition. Each condition has two biological replicates. Each hybridization represents expression levels of all 4,350 annotated genes with 20 60-mer oligonucleotides and with three technical replicates.

2013-01-22 | E-GEOD-43645 | biostudies-arrayexpress

The E3 ubiquitin ligase RNF115 regulates phagosome maturation and host response to infection

Project description:Phagocytosis is an essential process for the microbicidal function of professional phagocytes, in which phagosome maturation plays a critical role. Macrophage activation by interferons (IFN) increases their microbicidal activity, but delays phagosomal maturation. Here, we investigated the role of ubiquitylation in phagosome functions. We show that phagosomal proteins are ubiquitylated and that phagosomes contain diverse ubiquitin chain types, including atypical ubiquitin chains. IFN-γ activation of macrophages substantially enhanced phagosomal ubiquitylation of both innate immune response proteins and vesicle trafficking proteins. We identified the E3 ubiquitin ligase RNF115, which is enriched on phagosomes of IFN-γ activated macrophages, as an important regulator of phagosomal maturation. Loss of RNF115 protein or ubiquitin ligase activity facilitated enhanced phagosomal maturation, and increased cytokine responses to Staphylococcus aureus. Our data suggests that both innate immune signalling and phagolysosomal trafficking are controlled through ubiquitylation. In conclusion, we identify RNF115 and ubiquitylation as important regulators of innate immune signalling from the phagosome during bacterial infections.

2022-07-20 | PXD026843 | Pride

Phagosome proteome of mock and Atg8 silenced Entamoeba histolytica strains

Project description:The enteric protozoan parasite Entamoeba histolytica have high phagocytic ability. Phagocytosis is also important for the pathogenicity of this parasite; molecular mechanisms of phagocytosis and phagosome maturation is focused. Atg8 is well studied autophagy marker protein. We previously shown that E. histolytica Atg8 translocate to nascent trogosomes and expression silencing of the Atg8 caused retardation of phagosome acidification. To investigate how Atg8 regulates phagosome maturation, here we conducted proteome analysis of phagosomes isolated from an E. histolytica strain in which atg8 gene expression are silenced (atg8 gene silenced, atg8-gs) and its mock control strain (transfected with psAP2-Gunma).

2022-10-20 | PXD034376 | Pride

The Intracellular Life of Mycobacterium avium subsp. paratuberculosis During Macrophage Stress: A Key Role for the Alternative Sigma Factor, SigH

Project description:Mycobacterium avium subspecies paratuberculosis (a.k.a. M. paratuberculosis) causes JohneM-bM-^@M-^Ys disease, an enteric infection in cattle and other ruminants, greatly afflicting the dairy industry worldwide. Once inside the cell, M. paratuberculosis is known to survive harsh microenvironments, especially those inside activated macrophages. To improve our understanding of M. paratuberculosis pathogenesis, we examined the phagosome maturation associated with transcriptional responses of M. paratuberculosis during macrophage infection. Monitoring cellular markers, only live M. paratuberculosis bacilli were able to prevent phagosome maturation and reduce its acidification. On the transcriptional level, over 300 of M. paratuberculosis genes were significantly, differentially regulated in both naM-CM-/ve and IFN-M-NM-3-activated macrophages. These genes include the sigma factor H (sigH) that was shown to be important during persistent infection in M. tuberculosis. Interestingly, a sigH-knockout mutant showed increased sensitivity to a sustained level of thiol-specific oxidative stress. Large-scale RNA sequence analysis revealed that a large number of genes belong to the sigH regulon, especially following diamide stress. Genes involved in oxidative stress and virulence were among the induced genes in the sigH regulon with a putative consensus sequence for SigH binding was recognized in a subset of these genes (N=30), suggesting direct regulation with SigH. Finally, mice infections showed a significant attenuation of the M-bM-^HM-^FsigH mutant compared to its parental strain suggesting a role for sigH in M. paratuberculosis virulence. Such analysis could identify potential targets for further testing as vaccine candidates against JohneM-bM-^@M-^Ys disease. Examination of role played by alternative sigma factor, SigH during M. paratuberculosis infection.

2012-12-29 | E-GEOD-43182 | biostudies-arrayexpress