Quantitative analysis of pro-inflammatory cytokine mRNA expression in Theileria annulata-infected cell lines derived from resistant and susceptible cattle

McGuire, Kris; Manuja, Anju; Russell, George C.; Springbett, Anthea; Craigmile, Susan; Nichani, Anil; Malhotra, D.V.; Glass, Elizabeth J.

doi:10.1016/j.vetimm.2004.01.003

Cited by 51 publications

(36 citation statements)

References 40 publications

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“…In addition to AG490, transfection of a kinase-dead mutant of JAK2 leads to a reduction in c-Myc (Figure 3e) and transfection of two different dominant-negative mutants of STAT3 also decreased c-myc-driven luciferase activity, reinforcing the notion that this JAK/STAT3 signalling pathway contributes to c-myc activation (Figure 3e and f). Although we have clearly demonstrated that GM-CSF contributes to induction of c-myc transcription, we do not exclude that other gp130-dependent cytokines such as IL-6 potentially secreted by Theileria-transformed lymphocytes (McGuire et al, 2004) could also activate JAK2 and c-myc, via yet-to-be described autocrine loops. Indeed, we strongly suspected that other cytokines might be maintaining JAK2 and c-Myc activated, since specific inhibition of GM-CSF reduced proliferation, but did not generate apoptosis (Baumgartner et al, 2000).…”

Section: Discussionmentioning

confidence: 60%

c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes

et al. 2004

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Section: Discussionmentioning

confidence: 60%

c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes

et al. 2004

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“…RNA samples were extracted at day 0, 10, 12, 14 and 16 post tick challenge. One microgram of total RNA was treated with DNase I (Invitrogen) to remove residual DNA, and cDNA was synthesized from the total RNA with moloney murine leukemia virus (M-MLV) reverse transcriptase (TAKARA, Otsu, Japan) using oligo(dT) 18 primer (Hokkaido System Science, Sapporo, Japan). The quality and quantity of RNA was determined by measuring OD at 260 nm and agarose gel electrophoresis.…”

Section: Generation Of T Parva-infected Adult R Appendiculatus Ticksmentioning

confidence: 99%

Quantitative Analysis of Cytokine mRNA Expression and Protozoan DNA Load in Theileria parva-Infected Cattle

Yamada

Konnai

Imamura

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. Theileria parva (T. parva) causes a highly serious bovine disease called East Coast fever (ECF), which is characterized by pyrexia, dyspnea and cachexia and is of great economic importance in African countries. We hypothesize that the clinical symptoms of ECF could be explained by a cytokine dysregulation. In this study, we investigated the relationship between T. parva DNA load and expression levels of cytokine mRNAs in leukocytes from experimentally infected calves by quantitative PCR. The p104 gene, which encodes the T. parva 104 kDa microneme-rhoptry protein, was detected in cattle blood from day 10 after T. parva-infected tick infestation, and the protozoan DNA load was increased together with severity of disease. The mRNA expressions of pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-6, were up-regulated with protozoan DNA load increasing. In addition, the level of a type-2 cytokine (IL-10) transcript was also increased during the acute phase. In contrast, the down-regulation or no detectable levels of the expression of type-1 cytokines, such as IL-2 and interferon (IFN)-γ were observed in T. parva-infected animals. Thus, our observations indicated that high protozoan load and resulting intense inflammatory responses might be involved in the severity of clinical signs observed in T. parva-infection.

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“…We chose to use macrophages infected with T . annulata , which were recently isolated [22] from Holstein cattle susceptible for tropical Theileriosis because they display an aggressive invasive behavior in vitro [10], which correlates with more virulent disease progression in vivo . Using these cells as a model system for rounded/amoeboid matrix invasion, we described a novel mode of invasive cell motility that involves the extension of filopodia-like membrane protrusions at the leading edge and subsequent matrix expansion by membrane blebs…”

Section: Introductionmentioning

confidence: 99%

Filopodia and Membrane Blebs Drive Efficient Matrix Invasion of Macrophages Transformed by the Intracellular Parasite Theileria annulata

Baumgärtner

2013

PLoS ONE

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Recent technical advances have broadened our understanding of processes that govern mammalian cell migration in health and disease but many of the molecular and morphological alterations that precede and accompany movement of cells – in particular in three-dimensional (3D) environments - are still incompletely understood. In this manuscript, using high-resolution and time-lapse microscopy imaging approaches, we describe morphodynamic processes during rounded/amoeboid cell invasion and molecules associated with the cellular invasion structures. We used macrophages infected with the intracellular protozoan parasite Theileria annulata, which causes Tropical Theileriosis in susceptible ruminants such as domestic cattle. T . annulata transforms its host cell that, as a result, acquires many characteristics of human cancer cells including a markedly increased potential to migrate, disseminate and expand in the body of the host animal. Hence, virulence of the disease is associated with the capability of infected cells to disseminate inside the host. Using T . annulata -transformed macrophages as a model system, we described a novel mode of rounded/amoeboid macrophage migration. We show that filopodia-like membrane extensions at the leading edge lead the way and further evolve in blebbing membrane protrusions to promote progressive expansion of the matrix. Associated with focal invasion structures we detected ezrin, radixin, moesin-family proteins and their regulatory kinase MAP4K4. Furthermore, we linked Rho-kinase activity to contractile force generation, which is essential for infected cell motility. Thus, the motility mode of these parasite-transformed macrophages contrasts with those described so far in human macrophages such as the tunneling or mesenchymal modes, which require engulfment, compaction and ingestion of matrix or proteolytic matrix degradation, respectively. Together, our data reveal protrusion dynamics at the leading edge of invading cells in 3D at unprecedented temporal and spatial resolution and suggest a novel mode of rounded/amoeboid invasive cell motility that exploits actin-driven filopodia formation in combination with pressure-driven membrane blebs.

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Quantitative analysis of pro-inflammatory cytokine mRNA expression in Theileria annulata-infected cell lines derived from resistant and susceptible cattle

Cited by 51 publications

References 40 publications

c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes

c-Myc activation by Theileria parasites promotes survival of infected B-lymphocytes

Quantitative Analysis of Cytokine mRNA Expression and Protozoan DNA Load in Theileria parva-Infected Cattle

Filopodia and Membrane Blebs Drive Efficient Matrix Invasion of Macrophages Transformed by the Intracellular Parasite Theileria annulata

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