Strain hypothesis of Toxoplasma gondii infection on the outcome of human diseases

Abstract

The intracellular protozoan Toxoplasma gondii is an exceptionally successful food- and waterborne parasite that infects approximately 1 billion people worldwide. Genotyping of T. gondii isolates from all continents revealed a complex population structure. Recent research supports the notion that T. gondii genotype may be associated with disease severity. Here, we (1) discuss molecular and serological approaches for designation of T. gondii strain type, (2) overview the literatures on the association of T. gondii strain type and the outcome of human disease, and (3) explore possible mechanisms underlying these strain specific pathology and severity of human toxoplasmosis. Although no final conclusions can be drawn, it is clear that virulent strains (e. g. strains containing type I or atypical alleles) are significantly more often associated with increased frequency and severity of human toxoplasmosis. The significance of highly virulent strains can cause severe diseases in immunocompetent patients and might implicated in brain disorders such as schizophrenia should led to reconsideration of toxoplasmosis. Further studies that combine parasite strain typing and human factor analysis (e.g. immune status and genetic background) are required for better understanding of human susceptibility or resistance to toxoplasmosis.

Toxoplasma gondii infection in the context of the risk of schizophrenia development

“…Thirdly, the host immune response to T. gondii may affect expression of cytokines and the kynurenic acid pathway, both of which are implicated in the pathogenesis of schizophrenia. Finally, T. gondii does not induce symptoms directly, but through interactions with other factors, such as genetic susceptibility and/ or environmental factors (25).…”

“…Tissue cysts become established in various cells, particularly in long-lived differentiated cells, such as neurons and muscle cells, thereby ensuring long-term infection. In humans, T. gondii has tropism for the brain, which may influence the occurrence of certain mental disorders, including schizophrenia, personality disorders, dementia, and suicidal tendencies (25).…”

Adaptive and genetic evolution of Toxoplasma gondii: a host-parasite interaction

“…It is known that many atypical genotypes differ in pathogenicity and transmissibility from typical genotypes 11 , which allow us to propose a possible link between the infection in humans and genotypic profile of T. gondii strain.…”

“…Therefore, in response to the parasite's manipulation caused by the invasion of lesions sites, or biochemical signals, infected hosts show more active behavior, and reduced neophobic behavior, making the parasite more prone to completing its life cycle. T. gondii is able to determine a delicate balance between parasitism and the host's immune response, which is supported by the mode of infection, strain, immune and cytokine response, as well the interaction of host genes and parasite genes 10,11 , characterizing a behavioral manipulation, and conferring a selective advantage to T. gondii. In other words, T. gondii is an opportunistic parasite for humans and other animals (i.e., cats and dogs), as published before.…”

Toxoplasma gondii Tissue Cyst: Cyst Wall Incorporation Activity and Matrix Cytoskeleton Proteins Paving the Way to Nutrient Acquisition

“…However, T. gondii has been associated with an increase in the incidence of many relevant psychiatric disorders. This relates to the fact that the brain is an immune-privileged site for lifelong existence of T. gondii tissue cysts [2]. Although the current pharmacological treatments have been ineffective against the cyst form, it is possible that the tissue cyst wall acts as a biological barrier preventing the interaction of drugs with intracystic bradyzoites [3].…”