Characterisation of NF-κB complexes in  -transformed T cells

Machado, Joel; Fernández, Paula; Baumann, Ina; Dobbelaere, Dirk

doi:10.1016/s1286-4579(00)01284-3

Cited by 19 publications

(12 citation statements)

References 68 publications

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“…Nevertheless, the effect of this parasite occurs independently of PKB, unlike the results we report here for Toxoplasma. Furthermore, anti-apoptotic effects of Theileria depend upon NFB signaling (Machado et al, 2000) but we, and others, do not detect activation of this signaling pathway in infected MØs (Butcher et al, 2001;Shapira et al, 2002). In addition, infected lymphocytes undergo apoptosis dependent upon caspase-3 and , MØs were serum-starved for 18 hours after which wortmannin (WM), LY294002 (Ly) or solvent alone (DMSO) were added.…”

Section: Discussionmentioning

confidence: 60%

Toxoplasma gondiitriggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis

Kim

Denkers

2006

Journal of Cell Science

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Infection with the intracellular parasite Toxoplasma gondii renders cells resistant to multiple pro-apoptotic signals, but underlying mechanisms have not been delineated. The phosphoinositide 3-kinase (PI 3-kinase) pathway and the immediate downstream effector protein kinase B (PKB/Akt) play important roles in cell survival and apoptosis inhibition. Here, we show that Toxoplasma infection of mouse macrophages activates PKB/Akt in vivo and in vitro. In a mixed population of infected and non-infected macrophages, activation is only observed in parasite-infected cells. The PI 3-kinase inhibitors wortmannin and LY294002 block parasite-induced PKB phosphorylation. PKB activation occurs independently of Toll-like receptor adaptor protein MyD88 but uncoupling of Gi-protein-mediated signaling with pertussis toxin prevents PKB phosphorylation. Moreover, in the presence of PI 3-kinase inhibitors or pertussis toxin, not only PKB activation but also ERK1/2 activation during T. gondii infection is defective. Most importantly, the parasite's ability to induce macrophage resistance to pro-apoptotic signaling is prevented by incubation with PI 3-kinase inhibitors. This study demonstrates that T. gondii exploits host Gi-protein-dependent PI 3-kinase signaling to prevent induction of apoptosis in infected macrophages.

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Section: Discussionmentioning

confidence: 60%

Toxoplasma gondiitriggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis

Kim

Denkers

2006

Journal of Cell Science

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“…Alternatively, p100 may act predominantly as an inhibitory mechanism by forming high molecular weight complexes that bind pre-formed NFκB dimers thus serving as a molecular “buffer” to regulate availability of active NFκB for transcription [63]. BW720c sensitive nuclear localisation of NFκB2 was defined for T. parva infected cells in a study by [64], but they did not detect NFκB2 in complex with DNA. These results highlight the existence of transcriptional control mechanisms for components of the NFκB signalling pathway that are influenced by the presence of a live parasite and which are additional to the mechanism(s) that directly induce constitutive activation.…”

Section: Resultsmentioning

confidence: 99%

A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression

et al. 2013

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Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner.

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“…However, T lymphocytes infected with T. parva , which also constitutively activate NF-κB, do express c-REL. Furthermore, c-REL-containing NF-κB complexes are translocated to the host cell nucleus (Machado et al, 2000). The prevention of nuclear translocation of NF-κB complexes containing c-REL by c-MAF would partly nullify the activity of the IκB signalosome and would suggest that the suppression of MAF transcription factors is important for T. annulata and T. parva survival within the host cell.…”

Section: Discussionmentioning

confidence: 99%

The protozoan parasite Theileria annulata alters the differentiation state of the infected macrophage and suppresses musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors

Jensen

Makins

Kaliszewska

et al. 2009

International Journal for Parasitology

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The tick-borne protozoan parasite Theileria annulata causes a debilitating disease of cattle called Tropical Theileriosis. The parasite predominantly invades bovine macrophages (mϕ) and induces host cell transformation by a mechanism that has not been fully elucidated. Infection is associated with loss of characteristic mϕ functions and phenotypic markers, indicative of host cell de-differentiation. We have investigated the effect of T. annulata infection on the expression of the mϕ differentiation marker c-maf. The up-regulation of c-maf mRNA levels observed during bovine monocyte differentiation to mϕ was suppressed by T. annulata infection. Furthermore, mRNA levels for c-maf and the closely related transcription factor mafB were significantly lower in established T. annulata-infected cell-lines than in bovine monocyte-derived mϕ. Treatment of T. annulata-infected cells with the theileriacidal drug buparvaquone induced up-regulation of c-maf and mafB, which correlated with altered expression of down-stream target genes, e.g. up-regulation of integrin B7 and down-regulation of IL12A. Furthermore, T. annulata infection is associated with the suppression of the transcription factors, Pu.1 and RUNX1, and colony stimulating factor 1 receptor (CSF1R) which are also involved in the regulation of monocyte/mϕ differentiation. We believe these results provide the first direct evidence that T. annulata modulates the host mϕ differentiation state, which may diminish the defence capabilities of the infected cell and/or promote cell proliferation. Musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors play an important role in cell proliferation, differentiation and survival; therefore, regulation of these genes may be a major mechanism employed by T. annulata to survive within the infected mϕ.

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Characterisation of NF-κB complexes in -transformed T cells

Cited by 19 publications

References 68 publications

Toxoplasma gondiitriggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis

Toxoplasma gondiitriggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis

A Bovine Lymphosarcoma Cell Line Infected with Theileria annulata Exhibits an Irreversible Reconfiguration of Host Cell Gene Expression

The protozoan parasite Theileria annulata alters the differentiation state of the infected macrophage and suppresses musculoaponeurotic fibrosarcoma oncogene (MAF) transcription factors

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