scholarly journals Dense granule protein, GRA64 interacts with host cell ESCRT proteins during Toxoplasma gondii infection

2021 ◽  
Author(s):  
Joshua Mayoral ◽  
Rebekah B. Guevara ◽  
Yolanda Rivera-Cuevas ◽  
Vincent Tu ◽  
Tadakimi Tomita ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Electron Tomography ◽  
Cell Activity ◽  
Dense Granule ◽  
Secreted Proteins ◽  
Toxoplasma Infection ◽  
Granule Protein ◽  
Novel Host ◽  
Toxoplasma Gondii Infection

The intracellular parasite Toxoplasma gondii adapts to diverse host cell environments within a replicative compartment that is heavily decorated by secreted proteins. In attempts to identify novel parasite secreted proteins that influence host cell activity, we identified and characterized a trans-membrane dense granule protein dubbed GRA64 (TGME49_202620). We found that GRA64 is on the parasitophorous vacuolar membrane (PVM) and is partially exposed to the host cell cytoplasm in both tachyzoite and bradyzoite parasitophorous vacuoles. Using co-immunoprecipitation and proximity-based biotinylation approaches, we demonstrate that GRA64 appears to interact with certain components of the host Endosomal Sorting Complexes Required for Transport (ESCRT). Genetic disruption of GRA64 does not affect acute Toxoplasma virulence in mice nor encystation as observed via tissue cyst burdens in mice during chronic infection. However, ultrastructural analysis of Dgra64 tissue cysts using electron tomography revealed enlarged vesicular structures underneath the cyst membrane, suggesting a role for GRA64 in organizing the recruitment of ESCRT proteins and subsequent intracystic vesicle formation. This study uncovers a novel host-parasite interaction that contributes to an emerging paradigm in which specific host ESCRT proteins are recruited to the limiting membranes (PVMs) of tachyzoite and bradyzoite vacuoles formed during acute and chronic Toxoplasma infection.

scholarly journals Strain-specific activation of the NF-κB pathway by GRA15, a novel Toxoplasma gondii dense granule protein

2011 ◽  
Vol 208 (1) ◽  
pp. 195-212 ◽  
Author(s):  
Emily E. Rosowski ◽  
Diana Lu ◽  
Lindsay Julien ◽  
Lauren Rodda ◽  
Rogier A. Gaiser ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Nuclear Translocation ◽  
Strain Differences ◽  
Dense Granule ◽  
Forward Genetics ◽  
Type I ◽  
Type Ii ◽  
Granule Protein

NF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB–mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule proteins can therefore join rhoptry proteins in T. gondii’s host cell–modifying arsenal.

scholarly journals Transcriptomic analysis reveals Toxoplasma gondii strain-specific differences in host cell response to dense granule protein GRA15

2018 ◽  
Vol 117 (9) ◽  
pp. 2785-2793 ◽  
Author(s):  
Qing Liu ◽  
Wen-Wei Gao ◽  
Hany M. Elsheikha ◽  
Jun-Jun He ◽  
Fa-Cai Li ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Cell Response ◽  
Dense Granule ◽  
Transcriptomic Analysis ◽  
Host Cell Response ◽  
Granule Protein

scholarly journals The Toxoplasma gondii Dense Granule Protein GRA7 Is Phosphorylated upon Invasion and Forms an Unexpected Association with the Rhoptry Proteins ROP2 and ROP4

2008 ◽  
Vol 76 (12) ◽  
pp. 5853-5861 ◽  
Author(s):  
Joe Dan Dunn ◽  
Sandeep Ravindran ◽  
Seon-Kyeong Kim ◽  
John C. Boothroyd
Keyword(s):  
Toxoplasma Gondii ◽  
Host Cell ◽  
Parasitophorous Vacuole ◽  
Opportunistic Pathogen ◽  
Dense Granule ◽  
Host Cells ◽  
Obligate Intracellular ◽  
Dense Granules ◽  
Obligate Intracellular Parasite ◽  
Granule Protein

ABSTRACT The obligate intracellular parasite Toxoplasma gondii infects warm-blooded animals throughout the world and is an opportunistic pathogen of humans. As it invades a host cell, Toxoplasma forms a novel organelle, the parasitophorous vacuole, in which it resides during its intracellular development. The parasite modifies the parasitophorous vacuole and its host cell with numerous proteins delivered from rhoptries and dense granules, which are secretory organelles unique to the phylum Apicomplexa. For the majority of these proteins, little is known other than their localization. Here we show that the dense granule protein GRA7 is phosphorylated but only in the presence of host cells. Within 10 min of invasion, GRA7 is present in strand-like structures in the host cytosol that contain rhoptry proteins. GRA7 strands also contain GRA1 and GRA3. Independently of its phosphorylation state, GRA7 associates with the rhoptry proteins ROP2 and ROP4 in infected host cells. This is the first report of interactions between proteins secreted from rhoptries and dense granules.

scholarly journals Selective and strain-specific NFAT4 activation by the Toxoplasma gondii polymorphic dense granule protein GRA6

2014 ◽  
Vol 211 (10) ◽  
pp. 2013-2032 ◽  
Author(s):  
Ji Su Ma ◽  
Miwa Sasai ◽  
Jun Ohshima ◽  
Youngae Lee ◽  
Hironori Bando ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dense Granule ◽  
Type I ◽  
Dependent Manner ◽  
Activated T Cells ◽  
Host Immune Responses ◽  
Dense Granules ◽  
Granule Protein ◽  
C Terminus ◽  
Toxoplasma Gondii Infection

Toxoplasma gondii infection results in co-option and subversion of host cellular signaling pathways. This process involves discharge of T. gondii effector molecules from parasite secretory organelles such as rhoptries and dense granules. We report that the T. gondii polymorphic dense granule protein GRA6 regulates activation of the host transcription factor nuclear factor of activated T cells 4 (NFAT4). GRA6 overexpression robustly and selectively activated NFAT4 via calcium modulating ligand (CAMLG). Infection with wild-type (WT) but not GRA6-deficient parasites induced NFAT4 activation. Moreover, GRA6-deficient parasites failed to exhibit full virulence in local infection, and the treatment of WT mice with an NFAT inhibitor mitigated virulence of WT parasites. Notably, NFAT4-deficient mice displayed prolonged survival, decreased recruitment of CD11b+ Ly6G+ cells to the site of infection, and impaired expression of chemokines such as Cxcl2 and Ccl2. In addition, infection with type I parasites culminated in significantly higher NFAT4 activation than type II parasites due to a polymorphism in the C terminus of GRA6. Collectively, our data suggest that GRA6-dependent NFAT4 activation is required for T. gondii manipulation of host immune responses to maximize the parasite virulence in a strain-dependent manner.

scholarly journals Novel roles of dense granule protein 12 (GRA12) in Toxoplasma gondii infection

2020 ◽  
Vol 34 (2) ◽  
pp. 3165-3178 ◽  
Author(s):  
Jin‐Lei Wang ◽  
Meng‐Jie Bai ◽  
Hany M. Elsheikha ◽  
Qin‐Li Liang ◽  
Ting‐Ting Li ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dense Granule ◽  
Granule Protein ◽  
Toxoplasma Gondii Infection

scholarly journals Prevalence and risk factors for Toxoplasma gondii infection in certified and non-certified pig breeding farms in the Toledo microregion, PR, Brazil

2010 ◽  
Vol 19 (3) ◽  
pp. 152-156 ◽  
Author(s):  
Piassa Franciele Rossandra ◽  
Jacqueline Baptista de Araújo ◽  
Ronaldo César da Rosa ◽  
Rodrigo José Mattei ◽  
Rodrigo Costa da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Toxoplasma Gondii ◽  
Human Infection ◽  
Control Measures ◽  
Rodent Control ◽  
Reproductive Disorders ◽  
Toxoplasma Infection ◽  
Pork Products ◽  
Toxoplasma Gondii Infection ◽  
Breeding Farms

Toxoplasma gondii infection has been diagnosed in pigs all over the world. Economical losses are generally related to reproductive disorders. Toxoplasma infection is also a matter of public health because tissue cysts of the parasite may remain in pork and pork products, and become sources of human infection. The objective of this study was to evaluate the frequency and risk factors associated with Toxoplasma infection in certified and non-certified pig breeding farms in the Toledo microregion, in the State of Paraná, Brazil which includes the cities of Toledo, Nova Santa Rosa, Sao José das Palmeiras and Sao Pedro do Iguaçu. Relative frequency of infection was 13.4%, independently of the type of farm. Logistic regression analysis showed that the following factors were associated with infection: absence of workers exclusive for each area of the farm, access of other animals to feeders and drinkers, lack of lids in drinkers, lack of rodent control measures, mean piglet number and weight at weaning per female.

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