PMID- 24478077 OWN - NLM STAT- MEDLINE DCOM- 20140408 LR - 20211021 IS - 1098-5522 (Electronic) IS - 0019-9567 (Print) IS - 0019-9567 (Linking) VI - 82 IP - 2 DP - 2014 Feb TI - A toxoplasma patatin-like protein changes localization and alters the cytokine response during toxoplasmic encephalitis. PG - 618-25 LID - 10.1128/IAI.00444-13 [doi] AB - 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 (DeltaTgPL1) during acute and early chronic infection, the localization change of TgPL1 in bradyzoites caused us to reevaluate the DeltaTgPL1 mutant during late chronic infection and in a toxoplasmic encephalitis (TE) mouse model. Mice infected with DeltaTgPL1 are more resistant to TE and have fewer inflammatory lesions than mice infected with the wild type and DeltaTgPL1 genetically complemented with TgPL1. This increased resistance to TE could result from several contributing factors. First, we found that DeltaTgPL1 bradyzoites did not convert back to tachyzoites readily in tissue culture. Second, a subset of cytokine levels were higher in DeltaTgPL1-infected mice, including gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), 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. FAU - Tobin Magle, Crystal AU - Tobin Magle C AD - Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wisconsin, USA. FAU - Pittman, Kelly J AU - Pittman KJ FAU - Moser, Lindsey A AU - Moser LA FAU - Boldon, Kyle M AU - Boldon KM FAU - Knoll, Laura J AU - Knoll LJ LA - eng GR - T32 AI007414/AI/NIAID NIH HHS/United States GR - GM072125/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131125 PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Cytokines) RN - 0 (Protozoan Proteins) RN - 0 (Virulence Factors) RN - EC 3.1.- (Phospholipases) SB - IM MH - Animals MH - Cytokines/*metabolism MH - Gene Deletion MH - Genetic Complementation Test MH - Host-Pathogen Interactions MH - Mice MH - Mice, Inbred C57BL MH - Phospholipases/genetics/*metabolism MH - Protozoan Proteins/genetics/*metabolism MH - Toxoplasma/*enzymology MH - Toxoplasmosis, Cerebral/*immunology MH - Virulence Factors/genetics/metabolism PMC - PMC3911373 EDAT- 2014/01/31 06:00 MHDA- 2014/04/09 06:00 PMCR- 2014/08/01 CRDT- 2014/01/31 06:00 PHST- 2014/01/31 06:00 [entrez] PHST- 2014/01/31 06:00 [pubmed] PHST- 2014/04/09 06:00 [medline] PHST- 2014/08/01 00:00 [pmc-release] AID - IAI.00444-13 [pii] AID - 00444-13 [pii] AID - 10.1128/IAI.00444-13 [doi] PST - ppublish SO - Infect Immun. 2014 Feb;82(2):618-25. doi: 10.1128/IAI.00444-13. Epub 2013 Nov 25.