A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis.
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 (ΔTgPL1) during acute and early chronic infection, the localization change of TgPL1 in bradyzoites caused us to reevaluate the ΔTgPL1 mutant during late chronic infection and in a toxoplasmic encephalitis (TE) mouse model. Mice infected with ΔTgPL1 are more resistant to TE and have fewer inflammatory lesions than mice infected with the wild type and ΔTgPL1 genetically complemented with TgPL1. This increased resistance to TE could result from several contributing factors. First, we found that ΔTgPL1 bradyzoites did not convert back to tachyzoites readily in tissue culture. Second, a subset of cytokine levels were higher in ΔTgPL1-infected mice, including gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), 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.
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Crystal
C
Tobin Magle
Kelly J
KJ
Pittman
Lindsey A
LA
Moser
Kyle M
KM
Boldon
Laura J
LJ
Knoll
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D017353:Gene Deletion; D005816:Genetic Complementation Test; D054884:Host-Pathogen Interactions; D051379:Mice; D008810:Mice, Inbred C57BL; D010740:Phospholipases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000201:enzymology*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D015800:Protozoan Proteins; D037521:Virulence Factors; D010740:Phospholipases