Dataset Information

A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis.

ABSTRACT: Toxoplasma gondii is an obligate intracellular parasite that forms a lifelong infection within the central nervous system of its host. The T. gondii genome encodes six members of the patatin-like phospholipase family; related proteins are associated with host-microbe interactions in bacteria. T. gondii patatin-like protein 1 (TgPL1) was previously determined to be necessary for parasites to suppress nitric oxide and prevent degradation in activated macrophages. Here, we show that in the rapidly replicating tachyzoite stage, TgPL1 is localized within vesicles inside the parasite that are distinct from the dense granules; however, in the encysted bradyzoite stage, TgPL1 localizes to the parasitophorous vacuole (PV) and cyst wall. While we had not previously seen a defect of the TgPL1 deletion mutant (?TgPL1) during acute and early chronic infection, the localization change of TgPL1 in bradyzoites caused us to reevaluate the ?TgPL1 mutant during late chronic infection and in a toxoplasmic encephalitis (TE) mouse model. Mice infected with ?TgPL1 are more resistant to TE and have fewer inflammatory lesions than mice infected with the wild type and ?TgPL1 genetically complemented with TgPL1. This increased resistance to TE could result from several contributing factors. First, we found that ?TgPL1 bradyzoites did not convert back to tachyzoites readily in tissue culture. Second, a subset of cytokine levels were higher in ?TgPL1-infected mice, including gamma interferon (IFN-?), tumor necrosis factor alpha (TNF-?), interleukin 6 (IL-6), and monocyte chemotactic protein 1 (MCP-1). These studies suggest that TgPL1 plays a role in the maintenance of chronic T. gondii infection.

SUBMITTER: Tobin Magle C

PROVIDER: S-EPMC3911373 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis.

Tobin Magle Crystal C Pittman Kelly J KJ Moser Lindsey A LA Boldon Kyle M KM Knoll Laura J LJ

Infection and immunity 20131125 2

Toxoplasma gondii is an obligate intracellular parasite that forms a lifelong infection within the central nervous system of its host. The T. gondii genome encodes six members of the patatin-like phospholipase family; related proteins are associated with host-microbe interactions in bacteria. T. gondii patatin-like protein 1 (TgPL1) was previously determined to be necessary for parasites to suppress nitric oxide and prevent degradation in activated macrophages. Here, we show that in the rapidly ...[more]

PMID: 24478077

Similar Datasets

Project description:BACKGROUND:Cytokines are effective molecules of immune reactions. They work in inflammatory sites as well as circulate in the blood. Cytokines in the cerebrospinal fluid have been suggested to be markers of autoimmune encephalitis and reflect disease progression. However, studies on blood cytokines in autoimmune encephalitis are scarce. We report a case presenting with serial changes in blood cytokine levels in a male patient with anti-contactin-associated protein 2 (Caspr2) encephalitis. CASE PRESENTATION:A 61-year-old man without systemic disease presented with ataxia and speech disturbance 1 week. After admission, he further developed visual hallucinations, psychosis, and consciousness deterioration. Brain magnetic resonance imaging and infection and tumor surveillances were negative. 18F-fluorodeoxyglucose positron emission tomography of brain revealed frontal and occipital hypometabolism and anterior cingulate gyrus and mesial temporal hypermetabolism. Autoimmune studies confirmed Caspr2 antibodies in his blood. After receiving a diagnosis of anti-Caspr2 encephalitis, the patient received steroids, plasmapheresis, and zonisamide. He recovered well and was totally independent 6?months after disease onset. A cytokine profiler array kit was used to investigate neuroimmune mechanisms during the disease course. Several cytokines showed significant changes in plasma levels, such as B cell activating factor for B cell proliferation; thymus and activation-regulated chemokine for T cell chemoattraction; soluble CD40 ligand for Th2 cell mediation; C5/C5a for complement activation; brain-derived neurotrophic factor for neuronal survival response; and dipeptidyl peptidase 4, retinol binding protein, dickkopf-related protein, and epidermal growth factor for response to environmental provocation. The concentration of cytokines was verified using Luminex multiplexing assay. CONCLUSIONS:Due to their easy accessibility, blood cytokines are potential biomarkers of autoimmune encephalitis. Based on the investigating platform of this single case study, future larger scale studies are warranted.

Dataset Information

A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis.

Publications

A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets