Macrophage-parasite relationship in theileriosis. Reversible phenotypic and functional dedifferentiation of macrophages infected with <i>Theileria annulata</i>

Sager, Heinz; Davis, William C.; Dobbelaere, D. A. E.; Jungi, Thomas W.

doi:10.1002/jlb.61.4.459

Cited by 57 publications

(60 citation statements)

References 31 publications

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“…This cell transformation is closely related to the presence of the parasite within the host cell cytoplasm, as cells in which the parasite fails to establish itself during mitosis undergo apoptosis. Moreover, elimination of the parasites by the theilericidal drug buparvaquone leads to the cessation of proliferation and the dedifferentiation of the host cells to a resting phenotype (McHardy 1984, Sager et al 1997.…”

Section: Discussionmentioning

confidence: 99%

Identification, molecular characterization and subcellular localization of a Theileria annulata parasite protein secreted into the host cell cytoplasm

et al. 2007

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Intracellular leucoproliferative Theileria are unique as eukaryotic organisms that transform the immune cells of their ruminant host. Theileria utilize the uncontrolled proliferation for rapid multiplication and distribution into host daughter cells. The equal distribution of the schizont into the daughter cells is thought to be accomplished by a tight association with the host cell mitotic apparatus. In this study, we describe a highly conserved novel 37 kD Theileria annulata protein (TaSE). TaSE was found to be localized inside the parasite, the parasite membrane and within the host cell cytoplasm. Moreover, it co-localized at distinct points with host cell microtubules, which was especially apparent during mitosis, where co-localization was found with the centromere, the mitotic spindle and the midbody. Association of TaSE with the host cell tubulin network was corroborated by coimmunoprecipitation and transient transfection experiments. This is the first description of a theilerial protein co-localizing and potentially interacting with a host cell protein. The distribution of TaSE during mitosis makes it a protein to consider as playing a potential role for parasite distribution into daughter host cells.

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Section: Discussionmentioning

confidence: 99%

Identification, molecular characterization and subcellular localization of a Theileria annulata parasite protein secreted into the host cell cytoplasm

et al. 2007

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“…One reason for this is that ferret studies are hampered by a severe lack of immunological reagents. The ferret is a mustelid, and previous studies have identified cross-reactive monoclonal antibodies (mAbs) that bind mustelid proteins in mink (Aasted 1989, Danilenko et al, 1992, Jacobsen et al, 1993, Chen et al, 1997, Sager et al, 1997, Brodersen et al, 1998, Pedersen et al, 2002, Jensen et al, 2003, Saalmuller et al, 2005. These antibodies were originally generated against human, canine, ovine, and bovine cells.…”

Section: Introductionmentioning

confidence: 99%

Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection

Rutigliano

Doherty

Franks

et al. 2008

Journal of Immunological Methods

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Influenza virus infections carry a high public health cost, and pandemics are potentially catastrophic. Though the ferret is generally regarded as the best model for human influenza, no reagents are available for the analysis of cellular immunity. We thus screened monoclonal antibodies (mAbs) made for identifying immune cells in other species to see if any were cross-reactive. Flow cytometric analysis of lymphocytes isolated from blood, spleen, and lung of normal and virus-infected ferrets indicated that several mouse mAbs bound to the corresponding antigens in ferrets. Typing bronchoalveolar lavage populations from pneumonic ferrets with mAb to human CD8 showed the massive CD8+ T cell enrichment characteristic of this infection in mice. The availability of this, and several other mAbs that showed cross-reactivity, should allow us to begin the dissection of cellmediated immunity in the ferret, which, at least from these early results, looks similar to the situation in mice.

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“…To establish and survive, intracellular parasites modulate the host cell environment (42). Evidence that this process involves interfering with the molecular pathways that determine the phenotypes of mammalian cells is accumulating, and apicomplexan parasites have been shown to alter the control of cellular differentiation (29), proliferation (12), and apoptosis (21).…”

mentioning

confidence: 99%

“…A primary factor in the pathology of these diseases is the generation of neoplasia by rapidly dividing transformed infected leukocytes (6). Host cell division and dedifferentiation are induced by the intracellular multinucleated macroschizont stage (18,29) and are accompanied by alterations to bovine gene expression (30). These events are dependent on a viable macroschizont, as they can be reversed by the treatment of cells with the theileriacidal drug buparvaquone (22).…”

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confidence: 99%

A Theileria annulata DNA Binding Protein Localized to the Host Cell Nucleus Alters the Phenotype of a Bovine Macrophage Cell Line

et al. 2004

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The apicomplexan parasite Theileria annulata is the only intracellular eukaryote that is known to induce the proliferation of mammalian cells. However, as the parasite undergoes stage differentiation, host cell proliferation is inhibited, and the leukocyte is eventually destroyed. We have isolated a parasite gene (SuAT1) encoding an AT hook DNA binding polypeptide that has a predicted signal peptide, PEST motifs, nuclear localization signals, and domains which indicate interaction with regulatory components of the higher eukaryotic cell cycle. The polypeptide is localized to the nuclei of macroschizont-infected cells and was detected at significant levels in cells that were undergoing parasite stage differentiation. Transfection of an uninfected transformed bovine macrophage cell line, BoMac, demonstrated that SuAT1 can modulate cellular morphology and alter the expression pattern of a cytoskeletal polypeptide in a manner similar to that found during the infection of leukocytes by the parasite. Our findings indicate that Theileria parasite molecules that are transported to the leukocyte nucleus have the potential to modulate the phenotype of infected cells.

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Macrophage-parasite relationship in theileriosis. Reversible phenotypic and functional dedifferentiation of macrophages infected with Theileria annulata

Abstract: Abstract:Theileria annulata is a tick-transmilled pro-

Cited by 57 publications

References 31 publications

Identification, molecular characterization and subcellular localization of a Theileria annulata parasite protein secreted into the host cell cytoplasm

Identification, molecular characterization and subcellular localization of a Theileria annulata parasite protein secreted into the host cell cytoplasm

Screening monoclonal antibodies for cross-reactivity in the ferret model of influenza infection

A Theileria annulata DNA Binding Protein Localized to the Host Cell Nucleus Alters the Phenotype of a Bovine Macrophage Cell Line

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