Tumor Necrosis Factor Receptors and C-C Chemokine Receptor-2 Positive Cells Play an Important Role in the Intraerythrocytic Death and Clearance of .

is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune compromised state, age greater than 50, and asplenia.

Immune Mediators Important for a Protective Secondary Response to .

() is a tick-transmitted protozoan parasite that invades red blood cells. It is the primary cause of human babesiosis in the US. The severity of babesiosis caused by infection can range from asymptomatic to fatal.

Plasma Blood Levels of Tafenoquine following a Single Oral Dosage in BALBc Mice with Acute Infection That Resulted in Rapid Clearance of Microscopically Detectable Parasitemia.

Previous studies of mice infected with have shown that a single dose of tafenoquine administered orally is extremely effective at decreasing microscopically detectable parasitemia. However, a critical limitation of studies to date is the lack of data concerning the plasma levels of tafenoquine that are needed to treat babesiosis. In the current study, we begin to address this gap by examining the plasma levels of tafenoquine associated with the rapid reduction of patent parasitemia in a mouse model of babesiosis.

IFN-induced cell-autonomous immune mechanisms in the control of intracellular protozoa.

Vertebrate cells have evolved an elaborate multi-tiered intracellular surveillance system linked to downstream antimicrobial effectors to defend themselves from pathogens. This cellular self-defense system is referred to as cell-autonomous immunity. A wide array of cell-autonomous mechanisms operates to control intracellular pathogens including protozoa such as Toxoplasma gondii.

UBXN3B positively regulates STING-mediated antiviral immune responses.

The ubiquitin regulatory X domain-containing proteins (UBXNs) are likely involved in diverse biological processes. Their physiological functions, however, remain largely unknown. Here we present physiological evidence that UBXN3B positively regulates stimulator-of-interferon genes (STING) signaling.

Elimination of Is Dependent on Intraerythrocytic Killing and CD4 T Cells.

Babesiosis is a tick-borne zoonosis caused by protozoans of the genus , apicomplexan parasites that replicate within erythrocytes. However, unlike related species, the pathogenesis of infection remains poorly understood. The primary etiological agent of babesiosis in the United States is In healthy individuals, tick-transmitted infection with causes no specific clinical manifestations, with many having no symptoms at all.

Forward genetics screens using macrophages to identify Toxoplasma gondii genes important for resistance to IFN-γ-dependent cell autonomous immunity.

Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate intracellular protozoan pathogen. The parasite invades and replicates within virtually any warm blooded vertebrate cell type. During parasite invasion of a host cell, the parasite creates a parasitophorous vacuole (PV) that originates from the host cell membrane independent of phagocytosis within which the parasite replicates.

Identification of Toxoplasma gondii genes responsive to the host immune response during in vivo infection.

Toxoplasma gondii is an obligate intracellular protozoa parasite that causes the disease toxoplasmosis. It resides within host cells in a parasitophorous vacuole distinct from the host cell endocytic system. T.

Discovery of a novel Toxoplasma gondii conoid-associated protein important for parasite resistance to reactive nitrogen intermediates.

Toxoplasma gondii modifies its host cell to suppress its ability to become activated in response to IFN-γ and TNF-α and to develop intracellular antimicrobial effectors, including NO. Mechanisms used by T. gondii to modulate activation of its infected host cell likely underlie its ability to hijack monocytes and dendritic cells during infection to disseminate to the brain and CNS where it converts to bradyzoites contained in tissue cysts to establish persistent infection.

Toxoplasma gondii: determinants of tachyzoite to bradyzoite conversion.

Apicomplexa are primarily obligate intracellular protozoa that have evolved complex developmental stages important for pathogenesis and transmission. Toxoplasma gondii, responsible for the disease toxoplasmosis, has the broadest host range of the Apicomplexa as it infects virtually any warm-blooded vertebrate host. Key to T.

The role of specific Toxoplasma gondii molecules in manipulation of innate immunity.

Infection with the parasite Toxoplasma gondii stimulates an innate immune response in the host. T. gondii also induces alterations in infected monocytes and dendritic cells that probably contribute to its ability to disseminate and ultimately to establish persistent infection.

A transmembrane domain-containing surface protein from Toxoplasma gondii augments replication in activated immune cells and establishment of a chronic infection.

Toxoplasma gondii mutants identified as defective in the establishment of chronic infection were screened to isolate those specifically impaired in their ability to replicate within activated macrophages. One of the identified mutants contains an insertion in the hypothetical gene TGME49_111670. Genetic complementation restores the ability of the mutant to replicate in immune cells and produce cysts in the brains of mice.

Discovery of parasite virulence genes reveals a unique regulator of chromosome condensation 1 ortholog critical for efficient nuclear trafficking.

Eukaryotic parasites are a leading cause of morbidity and mortality worldwide, yet little is known about the genetic basis of their virulence. Here, we present a forward genetic screen to study pathogenesis in the protozoan parasite Toxoplasma gondii. By using modified signature-tagged mutagenesis, the growth of 6,300 T.

A patatin-like protein protects Toxoplasma gondii from degradation in activated macrophages.

The apicomplexan parasite Toxoplasma gondii is able to suppress nitric oxide production in activated macrophages. A screen of over 6000 T. gondii insertional mutants identified two clones, which were consistently unable to suppress nitric oxide production from activated macrophages.

Production of IL-12 by macrophages infected with Toxoplasma gondii depends on the parasite genotype.

Three clonal strain types (I, II, and III) of Toxoplasma gondii predominate worldwide. The outcome of infection in mice is highly dependent on the parasite genotype with type I strains being uniformly virulent, while types II and III are nonvirulent. Interactions with the innate immune response play a major role in determining the outcome of infection in the murine model.

A novel population of Gr-1+-activated macrophages induced during acute toxoplasmosis.

Macrophages are potent mediators of parasite control following in vitro activation, yet the subsets of mononuclear cells that contribute to resistance in vivo remain poorly defined. To identify effector cells that contribute to the control of Toxoplasma gondii during the initial stages of disseminated infection, we developed a low-dose intraperitoneal challenge model. A population of unusual macrophage-like cells was recruited to the peritoneal cavity during the first 4 days postinfection.