Disease Tolerance in Toxoplasma Infection

Abstract

Toxoplasma gondii is a successful protozoan parasite that cycles between definitive felid hosts and a broad range of intermediate hosts, including rodents and humans. Within intermediate hosts, this obligate intracellular parasite invades the small intestine, inducing an inflammatory response. Toxoplasma infects infiltrating immune cells, using them to spread systemically and reach tissues amenable to chronic infection. An intact immune system is necessary to control life-long chronic infection. Chronic infection is characterized by formation of parasite cysts, which are necessary for survival through the gastrointestinal tract of the next host. Thus, Toxoplasma must evade sterilizing immunity, but still rely on the host's immune response for survival and transmission. To do this, Toxoplasma exploits a central cost-benefit tradeoff in immunity: the need to escalate inflammation for pathogen clearance vs. the need to limit inflammation-induced bystander damage. What are the consequences of sustained inflammation on host biology? Many studies have focused on aspects of the immune response that directly target Toxoplasma growth and survival, commonly referred to as “resistance mechanisms.” However, it is becoming clear that a parallel arm of the immune response has evolved to mitigate damage caused by the parasite directly (for example, egress-induced cell death) or bystander damage due to the inflammatory response (for example, reactive nitrogen species, degranulation). These so-called “disease tolerance” mechanisms promote tissue function and host survival without directly targeting the pathogen. Here we review changes to host metabolism, tissue structure, and immune function that point to disease tolerance mechanisms during Toxoplasma infection. We explore the impact tolerance programs have on the health of the host and parasite biology.

Recombinant Toxoplasma gondii Ribosomal Protein P2 Modulates the Functions of Murine Macrophages In Vitro and Provides Immunity against Acute Toxoplasmosis In Vivo

“…The RH strain belonging to T. gondii type I (including the GT1 strain) can be isolated from humans and is considered the most virulent lineage in mice [ 82 , 83 ]. As an opportunistic parasite, T. gondii can survive in a healthy body and develop into chronic infections, whereas a devastating sequence can be caused in patients with a lower immunity [ 84 ]. Further research should evaluate the immune protection of rTgRPP2 in chronic infection individuals.…”

Toxoplasmosis of the central nervous system: Manifestations vary with immune responses

“…Toxoplasmosis is one of the more common parasitic zoonoses worldwide. Its causative agent, TG, is a successful protozoan parasite that cycles between definitive felid hosts and a broad range of intermediate hosts including animals and humans [6]. In the global human population, the prevalence of TG infection varies widely, ranging from 5% (in Zambia) [7] to 90% (in Paris and francophone West Africa) [8,9]; the average prevalence of TG infection is 10-47% in the UK and USA [9,10].…”

γδ T cells in malaria: a double‐edged sword

“…The observed pathogenic role of γδ T cells in ECM development was strictly dependent on the liver stage without affecting the intrahepatic development of the parasite or inhibiting parasite replication during the intraerythrocytic stage of infection [51]. In fact, a decreased pro‐inflammatory microenvironment was observed in TCRδ −/− livers, suggesting a mechanism of disease tolerance since the lack of immunopathology did not involve reduced parasite growth rate or load [80–82]. These findings raise some issues in the context of immunization studies and, consequently, in the balance between sterile immunity and inflammation‐induced immunopathology.…”