Differential Gamma Interferon- and Tumor Necrosis Factor Alpha-Driven Cytokine Response Distinguishes Acute Infection of a Metatherian Host with Toxoplasma gondii and Neospora caninum

Abstract

Toxoplasma gondii and Neospora caninum (both Apicomplexa) are closely related cyst-forming coccidian parasites that differ significantly in their host ranges and ability to cause disease. Unlike eutherian mammals, Australian marsupials (metatherian mammals) have long been thought to be highly susceptible to toxoplasmosis and neosporosis because of their historical isolation from the parasites. In this study, the carnivorous fat-tailed dunnart (Sminthopsis crassicaudata) was used as a disease model to investigate the immune response and susceptibility to infection of an Australian marsupial to T. gondii and N. caninum. The disease outcome was more severe in N. caninuminfected dunnarts than in T. gondii-infected dunnarts, as shown by the severity of clinical and histopathological features of disease and higher tissue parasite burdens in the tissues evaluated. Transcriptome sequencing (RNA-seq) of spleens from infected dunnarts and mitogen-stimulated dunnart splenocytes was used to define the cytokine repertoires. Changes in mRNA expression during the time course of infection were measured using quantitative reverse transcription-PCR (qRT-PCR) for key Th1 (gamma interferon KEYWORDS apicomplexan parasites, cytokines, real-time PCR, transcriptomics N eospora caninum and Toxoplasma gondii (Apicomplexa: Coccidia) are tissue cystforming parasites with a worldwide distribution. Although these closely related parasites share some similar morphological and biological features, they exhibit key differences in host range and pathogenicity (1, 2). Toxoplasma gondii is regarded as one of the most successful parasites due to its capacity to infect and cause disease in essentially any mammalian or avian species (3). In humans, it is also considered a pathogen of particular significance for pregnant and immunocompromised individuals (3, 4). In contrast, N. caninum is capable of infecting many different species but is not

NLRP3 Inflammasome Participates in Host Response to Neospora caninum Infection

“…Neosporosis often causes abortion especially in dairy cattle and leads to global economic losses ( 5 ); however, there is no treatment or vaccine available against this disease in cattle ( 6 ). Increasing attention has been paid to defining the role of the host immune response in N. caninum infection and to exploring the immune functions that influence control of infection and disease development ( 7 ). Host immune response against N. caninum infection is an essential determinant of neosporosis ( 1 , 6 , 8 ).…”

Seroprevalence of Toxoplasma gondii infection in arthritis patients in eastern China

“…Many of the clinical manifestations of acute toxoplasmosis are partially mediated by an overproduction of the patient’s pro-inflammatory cytokines, e.g. tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and interferon gamma (IFN-γ) [ 6 ], all of which are important in limiting the parasite’s growth [ 7 – 9 ].…”

T‐cell profiles elicited by Toxoplasma gondii in acutely/chronically infected humans

“…Furthermore, it was demonstrated that SAG1 is able to activate IL‐12 on APCs of both healthy and infected patients. This fact is a relevant for the design of therapeutic strategies (preventive and therapeutic vaccines), considering that this cytokine promotes Th1 polarization, which is involved in the control of T. gondii …”

“…The presence of IL‐12 and IFN‐γ is involved in the control of T. gondii infection . In contrast, a shift in bias towards a humoral Th2 immune response is associated with recrudescence of infection and uncontrolled parasite replication . Murine T lymphocytes, in the presence of SAG, produce IFN‐γ and IL‐12 and promote protection against challenge with a T. gondii .…”